Ultrasound localization system with advanced biopsy site markers

ABSTRACT

Disclosed biopsy markers are adapted to serve as localization markers during a surgical procedure. Adaptation includes incorporation of materials detectable under ultrasound during surgery, as well as features for co-registration with image guidance or other real-time imaging technologies during surgery. Such biopsy markers, when used as localization markers, improve patient comfort and reduce challenges in surgical coordination and surgery time. Additional disclosed biopsy markers are adapted to serve as monitoring and/or detection apparatuses. Localization of an implanted marker may be done with ultrasound technology. Ultrasound image data is analyzed to identify the implanted marker. A distance to the marker or a lesion may be determined and displayed. The determined distance may be a distance between the ultrasound probe and the marker or lesion, a distance between the marker or lesion and an incision instrument, and/or a distance between the ultrasound probe and the incision instrument.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/771,379, filed Jun. 10, 2020, now U.S. Pat. No. 11,234,772, which isa 35 U.S.C. § 371 National Stage Application of PCT/US2018/065010 filedon Dec. 11, 2018, which claims priority to U.S. Provisional PatentApplication No. 62/597,379, titled “Marker Localization UsingUltrasound” and filed on Dec. 11, 2017; U.S. Provisional PatentApplication No. 62/660,743, titled “Ultrasound Localization System” andfiled on Apr. 20, 2018; and U.S. Provisional Patent Application No.62/654,071, titled “Advanced Biopsy Markers” and filed on Apr. 6, 2018.Each of these applications are incorporated herein by reference in theirentireties. To the extent appropriate, a claim of priority is made toeach of the above disclosed applications.

BACKGROUND

In the diagnosis of breast cancer, a suspicious mass may be discoveredduring a preliminary examination involving visual examination,palpation, ultrasonic imaging, x-ray, magnetic resonance imaging (MRI),or other detection means. Thereafter, a biopsy procedure may beperformed to determine whether the suspicious mass is malignant orbenign. To minimize surgical intrusion, the biopsy procedure may involveinserting a small biopsy needle into the breast to extract one or moresamples (e.g., five samples) from locations around the mass and from thecenter of the mass. In one biopsy procedure, an ultrasound transducer ispositioned on the breast, typically with one hand and used to providevisual guidance to the medical professional performing the biopsy. Abiopsy needle held in the other hand of the medical professional isinserted it to the lesion location.

Regardless of the imaging modality or instrument used to perform thebiopsy procedure, subsequent examination of the biopsy site may benecessary, either in a follow up screening examination or for treatmentof a cancerous lesion. In order to mark the location of the lesion forsubsequent examination or treatment, a “biopsy site marker” may besurgically inserted during the biopsy procedure.

In its simplest form, a biopsy site marker serves as a landmark forfuture identification of a position of the lesion for treatment orfurther examination and is the standard of care for breast biopsy.However, due to limited advances in materials technology selection,manufacturing and deployment, paired with the high skill needed toidentify markers under different imaging modalities, traditional biopsysite markers suffer from a number of deficiencies, including poordetection under ultrasound or other visualization modalities, inabilityto co-register with surgical imaging modalities (e.g., an in-room imageguidance system, magnetic resonance imaging (MRI), etc.), lack ofon-going lesion monitoring capabilities, and lack of differentiationbetween the biopsy site marker and anatomical features of the patient.

If the biopsied site is cancerous, treatments may include mastectomy,lumpectomy, radiation therapy, or chemotherapy procedure that requirethe surgeon or radiologist to direct surgical or radiation treatment tothe precise location of the lesion. Surgical resection is the goldstandard, with more than 50% of cancer patients having surgicalprocedures. There are few successful technologies, and these areprimarily conducted ex vivo outside of the cavity, for determining themargin of a tumor (which happens mostly ex vivo outside of the cavity),which includes a rim of normal tissue surrounding the tumor. Ideallyduring resection, the surgeon intends to have ‘clear’ margins, i.e., thecomplete tumor surrounded by healthy tissue. Even so, upon removal, thesurgeon stains the resected tumor and sends it for frozen section to beassessed by a pathologist regarding whether the margins are actuallyclear or whether more tissue should be removed in a specificorientation. In aspects, such resection may occur days or weeks afterthe biopsy procedure, by which time the original features of the tissuemay have been removed or altered by the biopsy or may have changed dueto growth or progress of the lesion.

In order to mark the location of the lesion for resection, an additionallocalization procedure is performed prior to resection. With respect tolocalization, the patient must undergo an additional procedure, prior tosurgery, to insert a breast lesion localization wire at the biopsy site.The surgeon then uses the localization wire to advance to the cuttinginstrument to the site of the lesion to remove the lesion. Generally, aninterventional radiologist is required to deploy the wire under animaging modality just prior to surgery, for example x-ray. However,localization wires are not only uncomfortable but can also dislodge ormove as the stainless steel wire is protruding from the patient priorthe procedure. In addition, the use of a wire causes significantlogistical issues for the medical facility. For instance, a radiologistmust be available at a time slot directly prior to when a surgeon isavailable to perform the surgery. Such scheduling requirements are oftendifficult to achieve, and radiologists and surgeons may also be locatedin different buildings of a medical campus. In addition to the abovedeficiencies, traditional biopsy site markers are ill-equipped tomonitor the progression or regression of a lesion before, during orafter a surgical procedure or other treatment.

Wireless localization systems, such as radio frequency guidedlocalization, electromagnetic reflectors, magnetic tracers, andradioactive seed, are known, but suffer from a number of drawbacks. Allof which although may reduce patient discomfort, suffer the drawback ofhaving an additional step in the surgical workflow.

If the breast radiologist feels there is a chance that a finding ondiagnostic breast imaging is cancer, an image-guided breast biopsy willbe suggested. The current standard of care at the completion of a biopsyrecommends placement of a biopsy marker into the biopsied site. Thereare different types of biopsy markers but some are made of materialsthat have greater visibility under ultrasound than others. The markerserves multiple purposes. First, the marker serves to mark where thetissue was sampled in the breast. If the original area of interest is nolonger visible by imaging after the biopsy, the marker is a guide toknow where the diseased tissue was sampled. Second, if surgery isrecommended, the marker can be used as a target for the radiologist toplace the localization wire to the location of the marker. Third, thecancerous mass including the marker (and wire) removed during surgerymay then be imaged to ensure that the correct to show the mass wasaccurately removed from the breast.

It is with respect to these and other general considerations that theaspects disclosed herein have been made. Also, although relativelyspecific problems may be discussed, it should be understood that theexamples should not be limited to solving the specific problemsidentified in the background or elsewhere in this disclosure.

SUMMARY

Examples of the present disclosure describe systems and methods for thelocalization of an implanted marker through ultrasound technology alongwith additional combinations of other modalities.

In aspects, a first biopsy marker is provided. The biopsy markerincludes a central orb and a plurality of radial spokes connected at aproximal end to the central orb, where each of the plurality of radialspokes terminates at a distal orb. At least one of the plurality ofradial spokes is selectively positionable in a condensed configurationand in an expanded configuration. When in the condensed configuration,at least one of the plurality of radial spokes is folded in lateralalignment with a surface of the central orb; and when in the expandedconfiguration, at least one of the plurality of radial spokes protrudesradially from the surface of the central orb. The biopsy marker isconfigured for insertion at a biopsy site in the condensed configurationand is configured to deploy from the condensed configuration to theexpanded configuration upon insertion at a biopsy site. In some cases,the biopsy marker is configured to deploy into the expandedconfiguration based at least in part on shape-memory properties of amaterial from which the biopsy marker is made. The material may be analloy capable of reflecting ultrasound waves, such as Nitinol.Additionally, the biopsy marker may be configured for localization usingultrasonic imaging. In some cases, at least one distal orb of the biopsymarker includes a contrasting agent, which is configured to be releasedinto a biopsy site when impacted by ultrasound waves.

In further aspects, a second biopsy marker is provided. The biopsymarker includes a central core formed of a first material and at least afirst layer formed of a second material and surrounding the centralcore. In some cases, the second material may be configured to beactivated by ultrasound waves; and in other cases, the second materialmay include a chemotherapeutic drug that may be configured to becomesoluble when impacted by ultrasound waves. Alternatively, the secondmaterial may include a cancer-binding agent that is configured to bereleased when the second material is impacted by ultrasound waves.Alternatively still, the second material may include a rare earthmagnetic metal that is configured to be activated by ultrasound waves,an ingested agent, or an external remote control. When the secondmaterial is activated, the biopsy marker may be configured to alter ashape. In other case, the second material may be configured to beactivated by one or more changes in a bio-environment, such as a changein pH, a change in temperature, or a change in electrolyteconcentration. In response to one or more changes in thebio-environment, the second material may be configured to exhibitincreased fluoresce, increased solubility, increased echogenicity, arelease of a contrasting agent, or a release of a chemotherapeutic drug.When the central core is spherical, the second material may form aconcentric layer surrounding the central core. Additionally, a secondlayer formed of a third material may surround the first layer. The thirdmaterial may be different than the second material. In some aspects, thebiopsy marker may be configured for localization under ultrasonicimaging.

Further still, a third biopsy marker is provided. The biopsy markerincludes a fibrous polymer configured to be reactive to one or moreconditions of a bio-environment surrounding the fibrous polymer. The oneor more conditions of the bio-environment may include one or more of: atemperature, a pH, an electrolyte concentration and a blood flow. Thefibrous polymer may be configured to react to a condition of thebio-environment by one of: emitting heat, emitting visible light,fluorescing, increasing echogenicity, vibrating, shortening,lengthening, folding and thickening. In an example when the fibrouspolymer reacts by emitting heat, thermographic imaging of the biopsymarker may generate a heat map that may be indicative of a margin of thelesion. In aspects, the biopsy marker is configured to be injected neara lesion of a patient during a biopsy procedure.

In additional aspects, a method of determining information regarding alesion from a biopsy marker is provided. The method includes implantingthe biopsy marker during a biopsy procedure and activating the biopsymarker, where activating the biopsy marker may include delivering anagent to the biopsy marker, impacting the biopsy marker by ultrasoundwaves, or activating the biopsy marker using an external device. Thebiopsy marker may be activated in response to a change in abio-environment, where the change in the bio-environment may include achange in pH, a change in temperature, a change in blood flow or achange in electrolyte concentration. In aspects, the change inbio-environment may be indicative of a change in the lesion. The methodfurther includes receiving data from the biopsy marker and analyzing thereceived data, where analyzing the received data may include determininga location and/or an orientation of the biopsy marker. In some cases,determining the location and/or orientation of the biopsy marker may beperformed during a surgical procedure subsequent to the biopsyprocedure. Based on the analyzed data, the method includes determininginformation regarding the lesion, where determining informationregarding the lesion may include determining whether the lesion isprogressing or regressing or determining a margin of the lesion.

In an aspect, the technology relates to a method for localization of animplanted marker with ultrasound technology. The method includesemitting an array of ultrasonic sound waves from an ultrasonictransducer of an ultrasound probe; detecting reflected ultrasonic soundwaves by the ultrasonic transducer, wherein the reflected ultrasonicsound waves include at least a portion of the array of ultrasonic soundwaves after being reflected from a marker implanted proximate a lesionwithin an interior of a patient; and generating image data from thereflected ultrasonic sound waves. The method also includes analyzing, bya processor, the generated image data to identify the marker within theinterior of the patient; based at least in part on the identification ofthe marker, determining, by the processor, a distance to at least one ofthe marker or the lesion; and displaying, on a display operativelyconnected to the processor, the determined distance to the at least oneof the marker or the lesion.

In an example, the method includes displaying, on the display, anultrasound image including the marker based on the reflected ultrasonicsound waves. In another example, the determined distance to the at leastone of the marker or the lesion is displayed concurrently with theultrasound image. In yet another example, the marker is visuallydistinguished from a remainder of the ultrasound image by at least oneof: highlighting, outlining, a displayed indicator, or a color effect.In still another example, the determined distance to the at least one ofthe marker or the lesion is one of: a distance from a portion of theultrasound probe to the at least one of the marker or the lesion, adistance from a portion of a scalpel to the at least one of the markeror the lesion, or a distance from a portion of an incision instrument tothe at least one of the marker or the lesion. In still yet anotherexample, the incision instrument is one of a cautery tool, a scalpel, oran internal probe.

In another example, the method includes receiving a signal from a markerlocalization transceiver, wherein the marker localization transceiver isattached to the marker; processing, by the processor, the signalreceived from the marker localization transceiver to determine at leastone of a location of the marker or an orientation of the marker; andwherein determining the distance to the at least one of the marker orthe lesion is further based on the at least one of the location of themarker or the orientation of the marker. In yet another example, themethod includes receiving a signal from a probe localizationtransceiver, wherein the probe localization transceiver is attached tothe ultrasound probe; processing, by the processor, the signal receivedfrom the probe localization transceiver to determine at least one of alocation of the ultrasound probe or an orientation of the ultrasoundprobe; and wherein determining the distance to the at least one of themarker or the lesion is further based on the at least one of thelocation of the ultrasound probe or the orientation of the ultrasoundprobe. In still another example, the method includes receiving a signalfrom an instrument localization transceiver, wherein the instrumentlocalization transceiver is attached to an incision instrument;processing, by the processor, the signal received from the instrumentlocalization transceiver to determine at least one of a location of theincision instrument or an orientation of the incision instrument; andwherein determining the distance to the at least one of the marker orthe lesion is further based on the at least one of the location of theultrasound probe or the orientation of the ultrasound probe.

In another example, the determined distance includes a directionalcomponent. In yet another example, analyzing, by a processor, thegenerated image data to identify the marker within the interior of thepatient further comprises analyzing the generated image data usingpattern recognition techniques to identify the marker based on across-section of the marker. In still another example, the analyzing, bya processor, the generated image data to identify the marker furthercomprises identifying an orientation of the marker based on across-section of the marker. In still yet another example, thedetermining a distance to the marker within the interior of the patientis further based on the identified orientation of the marker.

In another aspect, the technology relates to a method for localizationof an implanted marker with ultrasound technology. The method includesemitting a first array of ultrasonic sound waves from an ultrasonictransducer of an ultrasound probe in a first position; detecting firstreflected ultrasonic sound waves by the ultrasonic transducer, whereinthe first reflected ultrasonic sound waves include at least a portion ofthe first array of ultrasonic sound waves after being reflected from amarker implanted within an interior of a patient; generating first imagedata from the first reflected ultrasonic sound waves. The method alsoincludes analyzing, by a processor, the generated first image data toidentify the marker within the interior of the patient. The methodfurther includes emitting a second array of ultrasonic sound waves fromthe ultrasonic transducer of the ultrasound probe in a second position;detecting second reflected ultrasonic sound waves by the ultrasonictransducer, wherein the second reflected ultrasonic sound waves includeat least a portion of the second array of ultrasonic sound waves afterbeing reflected from within the interior of the patient; generatingsecond image data from the first reflected ultrasonic sound waves; andanalyzing, by the processor, the generated second image data todetermine the marker is not present within the generated second imagedata. The method further includes generating a navigation indicator,wherein the navigation indicator indicates a direction of the markerrelative to the second position of the ultrasound probe; and displayingthe navigation indicator on a display concurrently with an ultrasoundimage generated from the second image data.

In an example, the method includes generating a first image from thefirst image data; and displaying the first image on a displayoperatively connected to the processor. In another example, the methodincludes based at least in part on the identification of the marker inthe generated first image data, determining a distance to the markerwithin the interior of the patient; and displaying on the display,concurrently with the display of the first image, the determineddistance to the marker. In yet another example, the determined distanceto the marker is one of: a distance from a portion of the ultrasoundprobe to the marker, a distance from a portion of a scalpel to themarker, or a distance from a portion of a cautery tool to the marker. Instill another example, the navigation indicator is an arrow pointing inthe direction of the marker relative the second position of theultrasound probe. In still yet another example, the method includesreceiving a signal from a marker localization transceiver, wherein themarker localization transceiver is attached to the marker; processing,by the processor, the signal received from the marker localizationtransceiver to determine at least one of a location of the marker or anorientation of the marker; and wherein generating the navigationindicator is further based on the at least one of the location of themarker or the orientation of the marker. In another example, the methodincludes receiving a signal from a probe localization transceiver,wherein the probe localization transceiver is attached to the ultrasoundprobe; processing, by the processor, the signal received from the probelocalization transceiver to determine at least one of a location of theultrasound probe or an orientation of the ultrasound probe; and whereingenerating the navigation indicator is further based on the at least oneof the location of the ultrasound probe or the orientation of theultrasound probe.

In another aspect, the technology relates to a system for ultrasoundlocalization. The system includes an implanted marker, wherein theimplanted marker is implanted in an interior of a patient; an ultrasoundprobe comprising an ultrasonic transducer, the ultrasonic transducerconfigured to emit an array of ultrasonic sound waves and detectreflected ultrasonic sound waves, wherein the reflected ultrasonic soundwaves include at least a portion of the array of ultrasonic sound wavesafter being reflected within an interior of a patient; a display; atleast one processor operatively connected to the display and theultrasound probe; and memory, operatively connected to the at least oneprocessor, storing instructions that when executed by the at least oneprocessor perform a set of operations. The set of operations includesgenerating image data from the reflected ultrasonic sound waves;analyzing, by a processor, the generated image data to identify themarker within the interior of the patient; based on the identificationof the marker and the reflected ultrasonic sound waves, determining adistance to at least one of the marker or the lesion; and displaying, onthe display, the determined distance to the at least one of the markeror the lesion.

In an example, the system also includes a marker localizationtransceiver attached to the marker, wherein the marker localizationtransceiver transmits data to indicate at least one of a location of themarker or an orientation of the marker. In another example, the systemalso includes a probe localization transceiver attached to theultrasound probe, wherein the probe localization transceiver transmitsdata to indicate at least one of a location of the probe or anorientation of the probe. In still another example, the system includesan incision instrument, wherein the incision instrument includes aninstrument localization transceiver, wherein the instrument localizationtransceiver transmits data to indicate at least one of a location of theincision instrument or an orientation of the incision instrument. In yetanother example, the incision instrument is one of a cautery tool, ascalpel, or an internal probe. In still yet another example, theinstrument localization transceiver is attached to a tip of the incisioninstrument.

In another example, at least one of the marker localization transceiver,the probe localization transceiver, or the instrument localizationtransceiver is a radio-frequency identification (RFID) device. In stillanother example, the system further comprises an inductive power source,wherein at least one of the marker localization transceiver, the probelocalization transceiver, or the instrument localization transceiver ispowered by the inductive power source.

In another aspect, the technology relates to a method for ultrasoundlocalization and navigation. The method includes emitting an array ofultrasonic sound waves from an ultrasonic transducer of an ultrasoundprobe; detecting reflected ultrasonic sound waves by the ultrasonictransducer, wherein the reflected ultrasonic sound waves include atleast a portion of the array of ultrasonic sound waves after beingreflected from an interior of a patient having an implanted markerproximate a lesion; generating image data from the reflected ultrasonicsound waves; and analyzing, by a processor, the generated image data todetermine whether the marker is present in the image data. The methodfurther includes based on the determination of whether the marker ispresent in the image data, perform at least one of: if the marker ispresent in the image data: determining, by the processor, a distance toat least one of the marker or the lesion; and displaying, on a displayoperatively connected to the processor, the determined distance to theat least one of the marker or the lesion; and if the marker is notpresent in the image data: determining the location of the marker;generating a navigation indicator, wherein the navigation indicatorindicates the location of the marker relative to a current position ofthe ultrasound probe; and displaying the navigation indicator on thedisplay concurrently with an ultrasound image.

In another aspect, the technology relates to a method for localizationof an implanted marker with ultrasound technology. The method includesemitting an array of ultrasonic sound waves from an ultrasonictransducer of an ultrasound probe; detecting reflected ultrasonic soundwaves by the ultrasonic transducer, wherein the reflected ultrasonicsound waves include at least a portion of the array of ultrasonic soundwaves after being reflected from a marker implanted proximate a lesionwithin an interior of a patient; generating image data from thereflected ultrasonic sound waves; displaying an ultrasound image fromthe generated image data; receiving user input to identify the marker inthe ultrasound image; based at least in part on the identification ofthe marker, determining, by the processor, a distance to at least one ofthe marker or the lesion; and displaying, on a display operativelyconnected to the processor, the determined distance to the at least oneof the marker or the lesion.

In an example, the method further includes identifying an incisioninstrument in the ultrasound image. In yet another example, identifyingthe incision instrument in the ultrasound image is based on user inputidentifying the incision instrument. In still another example, themethod further includes receiving input identifying a type of theincision instrument. In yet another example, identifying the incisioninstrument in the ultrasound image is based on the type of the incisioninstrument. In still yet another example, the method further includesreceiving input regarding a type of the marker. In another example, thedetermined distance is a distance between the incision instrument andthe marker. In yet another example, determining the distance is based onuser input drawing line between the incision instrument and the markeron the ultrasound image.

In another aspect, the technology relates to a method for confirmingmargins of a specimen. The method includes imaging the specimen from afirst orientation with an ultrasound probe, wherein the specimenincludes a lesion; determining the location of the lesion in the firstorientation; based on the location of the lesion, determining that amargin between the lesion and the edge of the specimen in the firstorientation is less than a predetermined margin; based on the marginbeing less than the predetermined margin, generating an alert. In anexample, determining the location of the lesion includes determining adistance from the ultrasound probe to the lesion. In another example,determining that the margin between the lesion and the edge of thespecimen in the first orientation includes comparing the location of theof the lesion to a predicted location of the lesion in the firstorientation. In yet another example, determining that the margin betweenthe lesion and the edge of the specimen in the first orientationincludes determining a difference between a distance from the ultrasoundprobe to the lesion and a distance from the lesion to a surface on whichthe lesion is placed. In still another example, the method furtherincludes rotating at least one of the specimen and the ultrasound probe;imaging the specimen from a second orientation with the ultrasoundprobe; determining the location of the lesion in the second orientation;based on the location of the lesion, determining that a margin betweenthe lesion and the edge of the specimen in the second orientation isless than the predetermined margin; based on the margin being less thanthe predetermined margin, generating another alert.

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter. Additionalaspects, features, and/or advantages of examples will be set forth inpart in the description which follows and, in part, will be apparentfrom the description, or may be learned by practice of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive examples are described with reference tothe following figures.

FIG. 1A depicts an example of an ultrasound localization system.

FIG. 1B depicts an example of the ultrasound localization system in usewith a patient.

FIG. 1C depicts an example of an ultrasound image including an implantedmarker.

FIG. 1D depicts an example of an ultrasound image not including theimplanted marker.

FIG. 1E depicts an example of a suitable operating environment forincorporation into the ultrasound localization system.

FIGS. 2A-2D depict an example biopsy site marker configured in acondensed and expanded three-dimensional radial-spoke shape.

FIG. 3 depicts an example biopsy site marker configured in amulti-layered spherical shape.

FIGS. 4A-4C depict an example biopsy site marker configured in anexpandable spherical lattice structure.

FIG. 5 depicts an example biopsy site marker configured as a fibrouspolymer.

FIG. 6 depicts an example method for determining information regarding alesion from an implanted marker.

FIG. 7A depicts an example method for localization of a lesion or animplanted marker.

FIG. 7B depicts an example of ultrasound imaging including a method ofcalculating distance from incision instrument to the marker.

FIG. 8A depicts another example method for localization and navigationto an implanted marker.

FIG. 8B depicts another example method for localization and navigationto an implanted marker.

FIG. 9 depicts an example method for localization and detection of animplanted marker and an incision tool.

FIG. 10A depicts an example system for imaging a specimen.

FIG. 10B depicts the ultrasound system of FIG. 10A with the specimenrotated.

FIG. 10C depicts the ultrasound system of FIG. 10A with the ultrasoundprobe rotated.

FIG. 11 depicts a method for confirming margins of a specimen.

FIGS. 12A-12F depict examples of implanted markers.

DETAILED DESCRIPTION

As discussed above, with respect to localization, the patient mustgenerally undergo an additional procedure to insert a breast lesionlocalization wire at the biopsy site. As detailed above, localizationwires are not only uncomfortable for the patient but cause significantlogistical issues for the medical facility.

As described herein, biopsy markers may be adapted to serve aslocalization markers during a surgical procedure. Prior biopsy sitemarkers serve as poor localization markers during a surgical procedurebecause they are not easily distinguished weeks or months afterplacement and are ill-equipped to monitor the progression or regressionof a lesion before, during or after a surgical procedure or othertreatment. The adaptation of biopsy site markers for localization mayinclude incorporation of various materials that are detectable underultrasound during surgery, as well as features for co-registration withimage guidance or other real-time imaging technologies during surgery.In this way, the use of biopsy markers, which are inserted with minimalintervention many days or weeks prior to a surgical procedure, improvepatient comfort and reduce challenges in surgical coordination andpatient time in surgery. Precise localization of the marker (e.g.,placement within 1 centimeter of the lesion) can increase the healthytissue left behind after removal of the tumor, whereas if the marker isdisplaced by even a few millimeters or centimeters from the correctlesion, it can cause excessive tissue removal leading to additionalsurgeries for complete removal or for optimizing cosmetic outcomes.

Additionally or alternatively, biopsy markers may be adapted to serve asmonitoring and/or detection apparatuses. For example, biopsy markers maybe equipped with a radio frequency identification (RFID) chip forsending and receiving data, global positioning (GPS) functionality fordetecting real-time marker positioning, features for co-registrationwithin a surgical room imaging field, pH meter or pH-reactive material,a magnetic seed or radioactive material contained within it, movementdetection functionality (e.g., via Doppler), vibration detectionfunctionality (e.g., via ultrasound elastography), thermal detectionfunctionality or a thermo-reactive material, electrolyte monitoringfunctionality, tumor recognition functionality (e.g., via antigenbinding, secretion detection, blood-flow or blood-pressure monitoring,etc.), and the like. It is with respect to these and other biopsy markeradvances that the present disclosure is directed.

In addition, prior solutions to localization of lesions through the useof stainless steel wires have several disadvantages ranging from patientdiscomfort to medical facility logistics. As an example, the use of astainless steel wire requires substantial additional medical facilityutilization on the day of surgery. For instance, on the day of surgery,a patient and any imaging modalities must first be prepped in radiology.A radiologist must then be available to insert the wire under theimaging modality. Once the wire is inserted, it may need to be furtherimaged and secured to allow transfer of the patient to the operatingroom. After the patient is transferred to the operating room, thesurgeon is still unable to view a live visualization of the lesion.Instead, the surgeon is required to rely solely on the wire as a guideto the lesion. Even where non-wire solutions are implemented, such asthe use of a radioactive seed, a radiologist is still generally requiredfor insertion of the seed. In addition, the radioactive seed alsointroduces radiation into the patient. Similarly, other non-wiresolutions such as radio frequency guided, electromagnetic reflectors,and magnetic tracers also require the radiologist's time for theplacement of the non-wire technology prior to surgery.

Examples of the present technology improve upon the prior technologyrequiring a wire, by allowing a marker to be implanted at the lesionsite multiple days prior to a surgery as well as providing a livevisualization and localization of the marker during surgery. Forexample, the marker can be placed at the time of a biopsy, rather thannear the time of surgery. Further, a radiologist may no longer be neededin a pre-surgical procedure to place the wire or wireless localizationdevice. At the time of surgery, the surgeon is also able to obtain avisualization of the marker through the use of ultrasound. For example,an ultrasound imaging system can detect and identify the marker withinthe patient. Upon identification of the marker, a distance and/ordirection to the marker can be automatically determined and displayed tothe surgeon along with an ultrasound image. The distance and directionto the marker may be indicative of a distance from an ultrasound probeto the marker or a distance from a marker to an incision instrument,such as a cautery tool, scalpel, or internal probe. In addition, wherethe geometry of the marker and the geometry of the lesion are known, adistance to an edge of the lesion may also be generated. Accordingly,the surgeon is able to more accurately perform the surgical incisions toget to a lesion marked by the marker.

FIG. 1A depicts an example of an ultrasound localization system 100. Theultrasound localization system 100 includes an ultrasound probe 102 thatincludes an ultrasonic transducer 104. The ultrasonic transducer 104 isconfigured to emit an array of ultrasonic sound waves 106. Theultrasonic transducer 104 converts an electrical signal into ultrasonicsound, or ultrasound, waves 106. The ultrasonic transducer 104 may alsobe configured to detect ultrasonic sound waves, such as ultrasonic soundwaves that have been reflected from internal portions of a patient. Insome examples, the ultrasonic transducer 104 may incorporate acapacitive transducer and/or a piezoelectric transducer, as well asother suitable transducing technology.

The ultrasonic transducer 104 is also operatively connected (e.g., wiredor wirelessly) to a display 110. The display 110 may be a part of acomputing system, including processors and memory configured to produceand analyze ultrasound images. Further discussion of a suitablecomputing system is provided below with reference to FIG. 1E. Thedisplay 110 is configured to display ultrasound images based on anultrasound imaging of a patient. The ultrasound imaging performed in theultrasound localization system 100 is primarily B-mode imaging, whichresults in a two-dimensional ultrasound image of a cross-section of aportion of the interior of a patient. The brightness of the pixels inthe resultant image generally corresponds to amplitude or strength ofthe reflected ultrasound waves. Other ultrasound imaging modes may alsobe utilized.

The ultrasound probe 102 may also include a probe localizationtransceiver 108. The probe localization transceiver 108 is a transceiverthat emits a signal providing localization information for theultrasound probe 102. The probe localization transceiver 108 may includea radio frequency identification (RFID) chip or device for sending andreceiving information. For instance, the signal emitted by the probelocalization transceiver 108 may be processed to determine theorientation or location of the ultrasound probe 102. The orientation andlocation of the ultrasound probe 102 may be determined or provided inthree-dimensional components, such as Cartesian coordinates or sphericalcoordinates. The orientation and location of the ultrasound probe 102may also be determined or provided relative to other items, such as anincision instrument, a marker, a magnetic direction, a normal togravity, etc. With the orientation and location of the ultrasound probe102, additional information can be generated and provided to the surgeonto assist in guiding the surgeon to a lesion within the patient, asdescribed further below. While the term transceiver is used herein, theterm is intended to cover both transmitters, receivers, andtransceivers, along with any combination thereof.

FIG. 1B depicts an example of the ultrasound localization system 100 inuse with a patient 112. In aspects, the ultrasound localization system100 may be utilized during a surgical procedure. In other aspects, theultrasound localization system 100 may be utilized during an examinationor diagnostic procedure. The ultrasound probe 102 is in contact with aportion of the patient 112, such as a breast of the patient 112. In theposition depicted in FIG. 1B, the ultrasound probe 102 is being used toimage a portion of the patient 112 containing an irregularly shapedlesion 114. A marker 116 has been implanted at or near the lesion 114.In aspects, the marker 116 may be implanted at the lesion during or inassociation with a biopsy procedure prior to the surgical procedurediscussed herein. The marker 116 allows for the lesion 114 to belocalized through the use of the ultrasound localization system 100. Toimage the portion of the patient 112 containing the marker 116, theultrasonic transducer 104 emits an array of ultrasonic sound waves 106into the interior of the patient 112. A portion of the ultrasonic soundwaves 106 are reflected off internal components of the patient 112 aswell as the marker 116, when the marker 116 is in the field of view, andreturn to the ultrasound probe 102 as reflected ultrasonic sound waves120. The reflected ultrasonic sound waves 120 may be detected by theultrasonic transducer 104. For instance, the ultrasonic transducer 104receives the reflected ultrasonic sound waves 120 and converts theultrasonic sound waves 120 into an electric signal that can be processedand analyzed to generate ultrasound image data on display 110. The depthof the marker 116 or other objects in an imaging plane may be determinedfrom the time between a pulse of ultrasonic waves 106 being emitted fromthe ultrasound prove 102 and the reflected ultrasonic waves 120 beingdetected by the ultrasonic probe 102. For instance, the speed of soundis well-known and the effects of the speed of sound based on soft tissueare also determinable. Accordingly, based on the time of flight of theultrasonic waves 106 (more specifically, half the time of flight), thedepth of the object within an ultrasound image may be determined. Othercorrections or methods for determining object depth, such ascompensating for refraction and variant speed of waves through tissue,may also be implemented. Those having skill in the art will understandfurther details of depth measurements in medical ultrasound imagingtechnology.

In addition, multiple frequencies or modes of ultrasound techniques maybe utilized. For instance, real time and concurrent transmit and receivemultiplexing of localization frequencies as well as imaging frequenciesand capture frequencies may be implemented. The localization frequenciesmay be implemented for lesion or marker targeting and the imagingfrequencies implemented for ultrasonography. Utilization of thesecapabilities provide information to co-register or fuse multiple datasets from the ultrasound techniques to allow for a real-timevisualization of a marker 116 and medical images on the display 110. Theimaging frequencies and capture sequences may include B-mode imaging(with or without compounding), Doppler modes (e.g., color, duplex),harmonic mode, shearwave and other elastography modes, andcontrast-enhanced ultrasound, among other imaging modes and techniques.

As detailed above, the marker 116 may be implanted at or near the lesion114 prior to a surgical procedure. For instance, when the lesion wasdetected in patent 112, samples may have been taken by biopsy and thentested to determine whether the lesion was malignant or benign.Thereafter, if the lesion was determined to be malignant, treatmentand/or further examination may have been prescribed. Such treatment,including surgical removal, radiation therapy, or other targetedtherapy, may occur days or weeks after the biopsy procedure, by whichtime the original features of the tissue may have changed. Accordingly,the marker 116 may be inserted during the biopsy procedure for futureidentification of the location of the lesion 114. In this way, ratherthan requiring coordination and placement of a localization wire at thetime of surgery, the previously-inserted marker 116 may be utilized tolocalize the lesion. Thus, logistics and scheduling on the day ofsurgery are simplified, as well as reducing an overall surgical time forthe patient. Further benefits are realized because marker 116 may bespecially designed for detection using ultrasound or other imagingtechnologies to provide live imaging and lesion location data during thesurgical procedure.

In the example depicted, the marker 116 is in the shape of a cube. Byutilizing a marker 116 in the shape of a cube, the marker 116 can bemore easily detected in an ultrasound image because cube-shaped itemsshould not naturally occur within the human body. For similar reasons,other shapes that are unexpected to occur in the human body may also beused for the marker 116. For example, shapes that have symmetriessimilar to that of a cube or an elongated rectangular prism also allowfor determinations of orientation of the marker 116 based on across-section of the marker 116 appearing in a respective ultrasoundimage, as discussed in further detail below. Additionally,radially-symmetrical shapes, multi-layered spherical shapes orspherically-shaped lattice structures, none of which would be naturallyoccurring in the human body, could be used to differentiate the marker116 from surrounding anatomy and/or tissue. For example, the marker 116may be of a shape that has clear margins (the opposite of spicullated),is of homogenous echogenicity, is hyperechoic in nature, withoutposterior acoustic shadowing, and is wider rather than taller inappearance.

The marker 116 may also include a marker localization transceiver 118.The marker localization transceiver 118 is a transceiver that emits asignal providing localization information for the marker 116. The markerlocalization transceiver 118 may include a radio frequencyidentification (RFID) chip or device for sending and receivinginformation. For instance, the signal emitted by the marker localizationtransceiver 118 may be processed to determine the orientation orlocation of the marker 116. The orientation and location of the markerlocalization transceiver 118 may be determined or provided inthree-dimensional components, such as Cartesian coordinates or sphericalcoordinates. The orientation and location of the marker 116 may also bedetermined or provided relative to other items, such as an incisioninstrument 126, the ultrasound probe 102, a magnetic direction, a normalto gravity, etc. With the orientation and location of the marker 116,additional information can be generated and provided to the surgeon toassist in guiding the surgeon to a lesion within the patient, asdescribed further below.

In other aspects, marker 116 may include additional or alternativefunctionality. For instance, marker 116 may include one or more sensorsor other detectors for monitoring the progression or regression of thetumor. For instance, such sensors may include a pH sensor, a blood-flow(or blood-pressure) sensor, an electrolyte sensor (e.g., for detectinguptake of calcium ions, Ca2+), a thermo-sensor, a Doppler device, etc.Sensors associated with or incorporated into the marker 116 maycommunicate sensor data with one or more devices via marker localizationtransceiver 118 or another transceiver (not shown). The devices forreceiving the sensor data may be in communication with the localizationsystem 100 or may be in communication with an independent monitoringsystem. In some cases, the monitoring system may evaluate the sensordata during a surgical procedure, on a continuous or semi-continuousbasis between surgical treatments, or any combination thereof.Evaluating the sensor data may enable the monitoring system to detectchanges in the tumor. For instance, an increase in blood-flow orthermographic footprint may indicate that cellular metabolism orvascularization is increasing in the area of the tumor, which mayindicate a progression of the lesion. In contrast, a decrease inblood-flow or thermographic footprint may indicate a decrease incellular metabolism or vascularization and a corresponding regression ofthe lesion. Additionally or alternatively, sensor data that indicates areduction in pH, or an increase in calcium ion (Ca2+) uptake, at or nearthe tumor site may be indicative of tumor progression. As should beappreciated, an increase in pH and/or a decrease in calcium ion uptakeat or near the tumor site may be indicative of tumor regression.

In still other aspects, marker 116 may comprise an implantable chipincluding hardware and/or software for monitoring a lesion size andpathology. For instance, an implantable chip marker may be configuredwith hardware and software for monitoring one or more of the conditionsdescribed above utilizing one or more associated sensors. Additionallyor alternatively, the implantable chip marker may provide in-situdelivery of prescribed drugs or may deliver targeted radiation to alesion. In some cases, the implantable chip marker may be activated byultrasound waves or by an external remote control. The implantable chipmarker may further include a transceiver for sending and receiving datato or from an external computing device and/or display.

In some cases, an agent may be ingested (e.g., as a pill or otherformulation in the days or weeks before a surgical procedure) thatscouts out and activates marker 116. For example, marker 116 maycomprise a receptor surface compatible with the agent. Upon binding tothe receptor surface, the agent may activate marker 116 or the agentitself may be activated. In this way, marker 116 may serve as alocalization marker when activated by the agent. Alternatively, theagent may serve as a cancer-cell binding agent. After ingestion, theagent may scout out lesion 114 (or other cancerous tumors) and may bindto the surface of lesion 114. In aspects, the agent may exhibitproperties detectable by various imaging systems. For example, the agentmay fluoresce, may vibrate, may emit heat or visible light, may exhibithigh echogenicity, etc. In this way, the marker 116 and/or lesion 114may be localized by an ingested agent.

In one embodiment, the marker 116 is comprised of a marker material thatis substantially dehydrated in a pre-deployment configuration and thatis configured to expand when exposed to fluid following deployment. Themarker material may be further configured to remain substantiallyphysically stable when implanted for an extended period of time (e.g.,from the biopsy procedure until at least one subsequent surgicalprocedure). In addition to being formed into a recognizable shape, asdetailed above, the marker material may be configured to reflectultrasound in a way that the marker 116 is recognizable as beingartificial. For example, the marker 116 may be reflective enough fordetection, but may not significantly block any anatomy underneath it.For example, the ultrasound-reflective material may be Nitinol. Nitinolis an alloy comprised of nickel and titanium arranged in a crystallinelattice. The crystalline lattice exhibits an ability to exist in twodifferent phases, known as martensite and austenite. The austenitearrangement is more compact and requires more energy to maintain so thatunder normal conditions Nitinol assumes the lower-energy, expandedmartensite arrangement. Due at least in part to this unique property,Nitinol exhibits shape-memory properties, which enables Nitinol to beformed into a first shape at a high temperature and, upon cooling, bereformed into at least one second shape. Thereafter, when heated above atransition temperature, the Nitinol resumes the first shape. Nitinol isgenerally provided as a wire, which may be woven into a wire mesh,braided, or otherwise shaped or configured.

The marker 116, various sensors, and/or the marker localizationtransceiver 118 may be powered via an inductive power supply 122. Theinductive power supply 122 generates an electromagnetic wave 124directed towards the marker 116. The marker 116 includes a coil, orsimilar receiver, capable of converting the electromagnetic wave 124 toelectric energy to power the marker 116 and/or the marker localizationtransceiver 118. The electromagnetic wave 124 may also be utilized as atrigger to activate or control the marker 116 and/or the markerlocalization transceiver 118. For example, receiving the electromagneticwave 124 by the marker localization transceiver 118 may trigger themarker localization transceiver 118 to send the signal providinglocalization information for the marker 116. In some examples, theultrasonic sound waves may trigger or activate the marker localizationtransceiver 118. In such examples, the inductive power supply may not benecessary, and the marker localization transceiver 118 may be powered bythe ultrasonic sound waves by converting the physical energy of thesound waves into electrical energy. In another example, a battery mayalso be used to power the marker localization transceiver 118. In stillanother example, the inductive power supply 122 may be incorporated intothe ultrasound probe 102. In such an example, the electromagnetic wave124 is emitted from the ultrasound probe 102.

An incision instrument 126 may also be utilized as part of theultrasound localization system 100. The incision instrument 126 may beany of a cautery tool, a scalpel, or other type of instrument used formaking incisions or intended for use within the interior of the patient112. For example, the incision instrument 126 may also be an internalprobe, such as a pH probe or a thermography probe. The incisioninstrument 126 may include an instrument localization transceiver 128.The instrument localization transceiver 128 is a transceiver that emitsa signal providing localization information for the incision instrument126. The instrument localization transceiver 128 may include a radiofrequency identification (RFID) chip or device for sending and receivinginformation. For instance, the signal emitted by the instrumentlocalization transceiver 128 may be processed to determine theorientation or location of the incision instrument 126. The orientationand location of the instrument localization transceiver 128 may bedetermined or provided in three-dimensional components, such asCartesian coordinates or spherical coordinates. The orientation andlocation of the incision instrument 126 may also be determined orprovided relative to other items, such as the marker 116, the ultrasoundprobe 102, a magnetic direction, a normal to gravity, etc. With theorientation and location of the incision instrument 126, additionalinformation can be generated and provided to the surgeon to assist inguiding the surgeon to a lesion within the patient, as described furtherbelow. The instrument localization transceiver 128 may also be poweredand/or trigger via the inductive power supply 122 in a similar manner asthe marker localization transceiver 118.

In an example, the instrument localization transceiver 128 is located atthe tip of the incision instrument 126. An indicator either on a display110 or on the incision instrument may indicate a distance from the tipof the incision instrument to the marker 116 or to an edge of the lesion114. Such a determination may be made from an analysis of ultrasounddata or information derived from the signals of the marker localizationtransceiver 118 and the instrument localization transceiver 128, or acombination thereof. In the case where the incision instrument 126 is acautery tool, the cautery tool may be configured to turn off when thetip of the cautery tool reaches the edge of the lesion 114. The distancebetween the tip of the incision instrument 126 and the edge of thelesion 114 and/or the marker 116 may also be determined where theinstrument localization transceiver 128 is not located in in the tip ofthe incision instrument 126. For example, where the size and shape ofthe incision instrument 126 is known, the location of the tip of theincision instrument 126 can be determined from the location andorientation of the instrument localization transceiver 128. In anexample, the respective distances may be determined based on the depthof the detected objects and the respective lateral distance between theobjects in the ultrasound image. As discussed above, depth to an objectmay be determined based on the time of flight of the ultrasound waves.The lateral distance between the two objects may be based on the amountof space between the objects in an ultrasound image. For instance, thelateral distance may be determined based on the number of pixels betweenthe two objects in the image. Lateral distance calculations andprocesses may be programmed into the ultrasound system 100. The lateraldistance calculations may also be trained with samples or phantomshaving markings with known distances. The lateral distance may then becalculated between any two objects appearing in the ultrasound image.Those having skill in the art will appreciate other processes andconsiderations for calculating lateral distances in ultrasound images.Once the depth of objects and lateral distances are determined, thedistance from one object to the other in two-dimensions orthree-dimensions may be determined through the use of trigonometricand/or geometric relationships between the lines used to measure thedepth and lateral distances.

Similarly, the location of the edge of a lesion can be determined fromthe location and orientation of the marker 116. For example, at the timethe marker 116 is inserted into the patient, the relative size and shapeof the lesion 114 may also be determined. When the marker 116 isinserted, the edge of the lesion 114 may be determined relative to thelocation and orientation of the marker 116. For instance, the edge ofthe lesion 114 may be represented as a function of the location andorientation of the marker 116. As such, in some examples, the marker 116need not be located directly at or on the lesion 114.

FIG. 1C depicts an example of an ultrasound image 130, including animage of the implanted marker 116, on the display 110. The ultrasoundimage 130 is an example of an ultrasound image where the marker 116 iswithin the field of view of the ultrasound probe 102. The ultrasoundimage 130 is generated from image data generated from the detectedreflected ultrasonic sound waves 120. Based on the image data or theultrasound image 130, the marker 116 is identified through the use ofimage analysis techniques. Because the shape of the marker 116 is not ashape that naturally occurs in the human body, image analysis techniquesare able to more easily detect and identify the marker 116 from theimage data. For instance, where the marker 116 is in the shape of acube, the marker 116 stands out as abnormal in ultrasound image data.Alternatively, the marker 116 may be indicated by a user in theultrasound image 130 once the marker 116 is within the field of view ofthe ultrasound probe 102.

The image analysis techniques may also be based on machine learningtechniques, such as neural networks, deep learning algorithms,statistical analysis techniques, enhanced contrast techniques, or otherpattern recognition or matching techniques that are trained based on theshape of the marker 116 implanted in the patient 112. As an example,where the shape of the marker 116 is a cube, the image analysisalgorithms may first be trained on a set of ultrasound images containinga cube-shaped marker in different orientations and cross-sectionalviews. Similar analysis may be achieved by recognizing or quantifyinggray scale changes (echogenicity grades) using machine learning. Thecurrent ultrasound image 130 or image data is then provided as an inputinto the trained image analysis algorithms to detect or identify themarker 116. Identifying the marker 116 is generally based on thecross-section of the marker as the ultrasound image 130 is atwo-dimensional image with a cross-section of the marker 116. In otheraspects, the marker 116 may be a three-dimensional radial-spoke shape, aspherically-shaped lattice structure or a multi-layered sphericalstructure surrounding a core material, none of which would be naturallyoccurring in the human body, could be used to differentiate the marker116 from surrounding anatomy and/or tissue. In this case, the trainedset of ultrasound images may comprise different orientations, differentgrey scale values, and cross-sectional views of the radial-spoke,multi-layered sphere or spherical lattice shapes.

In additional examples, an ultrasound technician or other user mayprovide additional input to assist in the identification of the marker116 in the ultrasound image. For example, input may be providedindicating the type of marker 116 that has been implanted in the patient112. The input may indicate the shape and size of the marker 116. In anexample, the input may include providing a model number or otheridentifying information for the marker 116. Based on the input, thedimensions and other information about the marker 116 may be obtained,such as from a local or remote database storing such information. Thedimensions of the marker, or other shape input, may then be used by theimage analysis techniques to assist in identification of the marker 116within the ultrasound image 130. The additional input from theultrasound technician or other user may also include directlyidentifying the marker 116 on the ultrasound image 130, such asreceiving pointer, touch, or other input to locate the marker 116. Forinstance, the ultrasound technician may select the marker 116 byclicking on the marker 116 with a mouse on a display of the ultrasoundimage 130. Distances to the marker 116 may then be based on the inputprovided by the ultrasound technician. For instance, the distance to themarker 116 may be determined based on the number of pixels in the imagebetween the marker and another point in the image. The input identifyingthe marker 116 (such as click on the image of the marker 116) may alsobe utilized in the image analysis techniques to limit the area of theultrasound image 130 to be analyzed. For example, upon receiving aselection of the marker 116 from an ultrasound technician, apredetermined area around the selection point may be analyzed toidentify the marker 116. In other examples, two-dimensional input (suchas box) may be provided by the ultrasound technician to provide aboundary for an area that is to be analyzed by the image analysistechniques to identify the marker 116.

The marker 116 may also be made from a material that makes the markereasier to detect within the ultrasound image 130 or image data. Forinstance, the material of the marker 116 may be selected to be amaterial that has a high degree of echogenicity, such as Nitinol. Byforming the marker 116 of a material having a high degree ofechogenicity, the marker 116 will appear brighter in the resultingultrasound image as materials with higher degrees of echogenicity have ahigher ability to reflect ultrasound waves. The marker 116 may also haveseveral flat like surfaces that may aid in the reflection of theacoustic waves, without blocking the anatomy underneath the marker 116(which could complicate later follow up). In some examples,incorporating air or other gases into the marker 116 may cause themarker 116 to appear brighter in the ultrasound image 130.

The marker 116 may be constructed to provide additional indicators toassist the surgeon in finding the marker 116. For example, the marker116 may include fluorescent materials or luminescent materials that emitvisible light so the surgeon can see the marker 116 during surgery. Insome examples, the marker 116 may include microbubbles that burst due tothe ultrasonic sound waves, causing the release of luminescent material.Alternatively, the marker 116 may be include an ultrasound contrastingagent, magnetic resonance imaging (MRI) contrasting agent or air, forinstance, within orbs at distal ends of radial spokes. In otherexamples, the marker 116 may include a rare earth magnetic metal that isactivated in response to the ultrasound waves or by remote control. Instill other examples, the marker 116 may include a material that iscapable of converting the ultrasonic sound wave energy into light in thevisible spectrum. The marker 116 may also include a light source that ispowered by the inductive power supply 122, a battery, or some otherpower source. Similarly, the marker 116 may also provide acoustic orhaptic output to alert the surgeon to the location of the marker. Themarker 116 may include a piezoelectric crystal that is activated byultrasound waves to produce electricity for powering the marker 116, thevarious sensors and/or the marker localization transceiver 118. In someaspects, the piezoelectric-powered marker may send location data and/orcommands (e.g., via marker localization transceiver 118) to otherdevices, sensors, transceivers, etc.

In other aspects, marker 116 may be composed of or filled with amolecular agent that, upon activation by the ultrasound waves, may bereleased to bind to cancer cells of lesion 114 and/or to deliverchemotherapeutic agents to the site of lesion 114. When the molecularagent is detectable using a fluorescence or other probe, the specificcontours of a margin of the lesion 114 may be identified. For example, amulti-layered spherical marker may comprise different molecular agentswithin different layers for activation at different times.Alternatively, different layers of the multi-layered spherical markermay become soluble and may dissolve in response to different conditions,such as changes in pH and/or electrolyte levels (e.g., Ca²⁺). That is,the different layers of a multi-layered spherical marker may be formedof different materials that are reactive under different conditions.

In other examples, the marker 116 may be configured to vibrate, causingthe marker 116 to increase in temperature. Alternatively, the marker 116may be composed of a reactive polymer, which may increasing intemperature in response to changes in pH or electrolyte concentration(e.g., Ca²⁺). In such an example, thermography can be performed toassist in identification of the marker 116. For example, the reactivepolymer marker may generate a heat map for detecting specific contoursof the margin for lesion 114. A temperature probe may also be used asthe incision instrument 126 or in addition to the incision instrument126 to assist in localization of the marker 116.

Identifying the marker 116 may also include identifying, by a processorthrough image analysis techniques, a particular cross-section of themarker 116 in order to determine an orientation of the marker 116. Forinstance, in the ultrasound image 130, the orientation of the marker 116can be determined from its cross-section because the marker 116 is in acube shape. If the marker 116 has 360 degree rotational symmetry (suchas a sphere shape), such an orientation determination would be moredifficult. Other shapes for the marker 116 may also be used that havemore complex cross-sections and incomplete 360 degree rotationalsymmetry, such as for example, cones, star-shapes, pyramids, ovoids,tetratehedrons, tetrahemihexacrons a three-dimensional radial-spokeshape, a spherically-shaped lattice structure or a multi-layeredspherical structure surrounding a core material, and other shapes suchas those shown in FIGS. 10A-F. In such examples, the more intricateshapes may provide additional orientation information from theirrespective cross-sections. Considerations should be made, however, toensure that the selected shape is still distinguishable or identifiablefrom the remaining anatomy and/or tissues of the interior of the patient112.

In additional examples, the different faces of the marker 116 may bedistinguishable from one another based on sandblasting, patterning,numbering, lettering, or other features that may be able to bedistinguished in a resultant ultrasound image. The numbering,patterning, lettering, etc. may be raised, embossed, or made of adifferent material to cause the markings to be more visible in theultrasound image 130. For instance, as shown in FIG. 1C, an “A”indicator on the cross-section of the marker 116 can be seen in theultrasound image 130. Thus, the orientation of the marker 116 may bedetermined by detecting the indicator “A” in the ultrasound image 130.

If the marker 116 is detected or identified, as is the case withultrasound image 130, the marker 116 is highlighted or otherwiseemphasized in the ultrasound image 130. In some examples, the marker 116is highlighted with a particular color effect, having its brightnessincreased, or otherwise causing the marker to be highlighted. The marker116 may also be outlined with an artificial outline to emphasize thepresence of the marker 116. A graphical indicator may also be displayedon top of or proximate the marker 116. For example, an arrow may bedisplayed in the ultrasound image 130 pointing to the marker 116. Thecolor of the marker 116 may also be changed to further highlight oremphasize the marker 116 from the remainder of the ultrasound image 130.The highlighting or emphasis of the ultrasound may be accomplished bymodifying the ultrasound image itself or adding a layer on top of theultrasound image to achieve the desired highlighting or emphasis of themarker 116. Captured ultrasound images may also be fused withmammographic x-ray images (obtained after marker deployment or followup), in order to aid in the confirmation of the marker location andshape. The permanent metallic/ceramic materials of the markers havedistinct shape, therefore the fusion of ultrasound and x-ray isbeneficial to identify the specific marker in lesion of interest, asthere could be multiple lesions within one breast.

Other indicators may also be triggered when the marker 116 is identifiedand in the field of view. For instance, an audible sound, such as abeep, may be emitted when the marker comes within a field view. In someexamples, a tone having a varying frequency or intensity may also beemitted based on how close the marker 116 is to the center of the fieldof view. Lights or other visual indicators may also be displayed whenthe marker 116 comes into the field of view. Haptics (e.g., a vibratingelement) on the ultrasound probe 102 may also be activated when themarker 116 comes into the field of view.

Once the marker 116 has been identified and the distance to the lesion114 or the marker 116 has been determined, the determined distance isdisplayed on the display 110. For example, the distance may be displayedin a user interface element 132 on the display 110. Other techniques fordisplaying or otherwise providing an indication of the determineddistance are also possible, such as a dedicated indicator panel (e.g., aseven-segment display or a separate LCD screen) or an audible indicator.In other examples, the distance may be displayed or indicated on theultrasound probe 102 or the incision instrument 126.

The distance to the marker 116, and the orientation of the marker 116can then be used to guide the incision instrument 126 to the location ofthe marker 116 in order to excise the lesion. In one example, theorientation of the marker 116 could indicate to the user the point onwhich to start the incision. In another example, the distance to themarker 116 can be displayed as a vector on the ultrasound image 130 inorder to provide one possible path for the incision instrument 126 tofollow to remove the lesion. In another example, the distance to themarker 116 can be combined with the distance information about theincision instrument 126 to show whether the incision instrument 126 isclose to the marker 116. In some examples, that distance information ofthe incision instrument 126 can show whether the incision instrument isdeviating from the possible incision path.

In some cases, the ultrasound probe may be positioned such that themarker 116 is not within the field of view. FIG. 1D depicts an exampleof an ultrasound image 134 where the marker 116 is not within the fieldof view. In such an example, an ultrasound technician may be havingdifficulty locating the marker 116. As such, a navigation indicator 136may be displayed providing navigation guidance for the ultrasoundtechnician to find the marker 116. From the location and orientationinformation of the marker 116, based on the ultrasound identificationdiscussed above and/or a signal from the marker localization transceiver118, the navigation indicator 136 is illuminated to direct theultrasound technician to the marker 116. In the example depicted, thenavigation indicator 136 may include a series of arrows. Individualarrows may be highlighted to direct the ultrasound technician to movethe ultrasound probe in a particular direction. For instance, if themarker 116 is out of the field of view and moving the ultrasound probeto the left would cause the marker 116 to come into the field of view,the left arrow is illuminated. While the navigation indicator 136depicted is in the form of arrows, other types of navigation indicatorsmay be utilized to provide guidance to the ultrasound technician to findthe marker 116. For example, different graphical user interface elementsmay be displayed on the display 110. Other indicators may also beprovided in the ultrasound probe 102 itself to assist the technician infind the marker 116 and bringing the marker 116 into the field of view.In examples where the ultrasound probe 102 is automatically controlledand guided, such as by a robotic arm, the location of the marker 116 maybe used to automatically guide the ultrasound probe 102 to bring themarker 116 into the field of view.

FIG. 1E depicts an example of a suitable operating environment 150 forincorporation into the ultrasound localization system. In its most basicconfiguration, operating environment 150 typically includes at least oneprocessing unit 152 and memory 154. Depending on the exact configurationand type of computing device, memory 154 (storing instructions toperform the active monitoring embodiments disclosed herein) may bevolatile (such as RAM), non-volatile (such as ROM, flash memory, etc.),or some combination of the two. This most basic configuration isillustrated in FIG. 1E by dashed line 156. Further, environment 150 mayalso include storage devices (removable 158, and/or non-removable 160)including, but not limited to, magnetic or optical disks or tape.Similarly, environment 150 may also have input device(s) 164 such askeyboard, mouse, pen, voice input, etc. and/or output device(s) 166 suchas a display, speakers, printer, etc. The input devices 164 may alsoinclude one or more antennas to detect signals emitted from the varioustransceivers in the ultrasound localization system 100, such as theprobe localization transceiver 108, the marker localization transceiver118, and/or the instrument localization transceiver 128. Also includedin the environment may be one or more communication connections 162,such as LAN, WAN, point to point, etc. In embodiments, the connectionsmay be operable to facility point-to-point communications,connection-oriented communications, connectionless communications, etc.

Operating environment 150 typically includes at least some form ofcomputer readable media. Computer readable media can be any availablemedia that can be accessed by processing unit 152 or other devicescomprising the operating environment. By way of example, and notlimitation, computer readable media may comprise computer storage mediaand communication media. Computer storage media includes volatile andnonvolatile, removable and non-removable media implemented in any methodor technology for storage of information such as computer readableinstructions, data structures, program modules or other data. Computerstorage media includes, RAM, ROM, EEPROM, flash memory or other memorytechnology, CD-ROM, digital versatile disks (DVD) or other opticalstorage, magnetic cassettes, magnetic tape, magnetic disk storage orother magnetic storage devices, or any other non-transitory medium whichcan be used to store the desired information. Computer storage mediadoes not include communication media.

Communication media embodies computer readable instructions, datastructures, program modules, or other data in a modulated data signalsuch as a carrier wave or other transport mechanism and includes anyinformation delivery media. The term “modulated data signal” means asignal that has one or more of its characteristics set or changed insuch a manner as to encode information in the signal. By way of example,and not limitation, communication media includes wired media such as awired network or direct-wired connection, and wireless media such asacoustic, RF, infrared, microwave, and other wireless media.Combinations of the any of the above should also be included within thescope of computer readable media.

The operating environment 150 may be a single computer operating in anetworked environment using logical connections to one or more remotecomputers. The remote computer may be a personal computer, a server, arouter, a network PC, a peer device or other common network node, andtypically includes many or all of the elements described above as wellas others not so mentioned. The logical connections may include anymethod supported by available communications media.

FIG. 2A depicts an example biopsy site marker configured in athree-dimensional radial-spoke shape. As illustrated by FIG. 2A, in anexpanded configuration, the radial-spoke marker 200 may comprise acentral orb 202 from which a plurality of radial spokes 204 protrude. Inaspects, the radial spokes 204 may be orthogonal to one another withinthree-dimensional space, e.g., the spokes may radiate from the centralorb 202 along x, y, and z axes. In other examples, the radial spokes 204may be located at different angles from the central orb 202 and eachother. Each radial spoke 204 may be connected to the central orb 202 ata proximal end and may be connected to a distal orb 206 at a distal end.Any number of radial spoke 204 and distal orbs 206 are contemplated. Inone example, the central orb 202 may be hollow, in other examples it canbe solid, filled volume. In a condensed configuration shown in FIG. 2B,the radial spokes 204 may fold around or about the central orb 202 suchthat the radial spokes 204 are substantially laterally aligned with asurface of the central orb 202. In one example, the central orb 202 mayhave indents 208 to receive the distal orbs 206 in the surface of thecentral orb 202. For example, in its condensed configuration, the radialspoke marker 200 may be sized for delivery via an elongated needle aspart of a marker deployment device. Following insertion at the biopsysite, the radial-spoke marker 200 may deploy into the expandedconfiguration. Deployment into the expanded configuration may occur inresponse to removal of the mechanical force that keeps the distal orbscondensed in place, fluid present in patient 112, in response to thebody temperature of the patient 112, or otherwise.

For example, the radial-spoke marker 200 may be formed of Nitinol, whichmay be configured into a first shape (e.g., the expanded configuration)under heated conditions and configured into a second shape (e.g., thefolded or condensed configuration) under cooled conditions. Although theradial-spoke marker 200 may be delivered in the condensed configuration,it may “remember” the first shape and automatically deploy into theexpanded configuration based at least in part on the shape-memoryproperties of Nitinol. In one example, the radial-spoke marker 200 maybe comprised of a plurality of wires. The distal orbs 206 may be a solidshape or a shape containing openings and also be made of the Nitinolmaterial or made of different materials visible under ultrasound orother imaging modalities such as biocompatible titanium, polymers, gold,or stainless steel or other materials. In one example, the ends of theplurality of wires can fit inside the distal orbs 206 that would holdthem in place. Alternatively, the distal orbs 206 may be attached to theradial spokes 204. Each or some of the distal orbs 206 can be made ofdifferent materials than other distal orbs 206.

In additional or alternative aspects, the radial-spoke marker 200 may bedelivered in different sizes depending upon an initial (or baseline)size of the targeted lesion. In this way, a progression or regression ofthe lesion may be detected based on the size of the marker as comparedto the size of the lesion at the time of a surgical or other procedureperformed under ultrasound.

In some aspects, the lengths of the radial spokes 204 may be equal. Inother examples, the length of the radial spokes 204 may comprisedifferent lengths as shown in FIG. 2C. The different lengths of theradial spokes 204 (e.g., radial spokes 204A and 204B) may indicate tothe ultrasound system 100, the orientation of the marker 200. As thecross section (or the two-dimensional image) of the marker may vary. Insome aspects, the distal orbs 206 may comprise the same size. In otherexample, the distal orbs 206 may comprise different sizes and maysimilarly indicate orientation of the marker 200. In at least oneembodiment, each or some of the distal orbs can be patterned for exampleindents of different sizes can increase visibility under some imagingmodalities.

In some aspects, as illustrated by FIG. 2D, the central orb 202 can bemade of bio-absorbable material for example, hydrogel, blend and/orcopolymer of polyglycolide or polyglycolic acid. In this example thecentral orb 202 over time may be absorbed by the body, while the distalspheres, not comprising bio-absorbable material remain in the body.

In some aspects, one or more of the distal orbs 206 may be comprised ofor encompass a different material. For example, one or more distal orbs206 may comprise an MRI or ultrasound contrasting agent. Upon activationby ultrasound waves or magnetic resonance, the distal orbs may burst orotherwise release the contrasting agent. In this way, radial-spokemarker 200 may be co-registered within an ultrasound and an MRI imagingmodality. In other aspects, the radial-spoke marker 200 may be formed ofNitinol, or some other reflective material which could be a shape memorypolymer, which is discernable using ultrasonic imaging technologies. Instill other examples, one or more distal orbs 206 may comprise achemotherapeutic drug that is released to the site of a lesion uponactivation by ultrasound waves and/or MRI, or in response to some othercondition such as a change in temperature, change in pH, change inelectrolyte concentration, etc. In further examples, various distal orbs206 may react differently to an amount of radiation or chemotherapydelivered to the site of a lesion. In this way, the amount of treatmentdelivered to the lesion may be detected by radial-spoke marker 200. Insome cases, one or more distal orbs 206 may comprise a cancer-cellbinding agent that may be released in response to ultrasound wavesand/or changes in conditions, as described above. Such cancer-cellbinding agent may have properties capable of imaging to enable mappingof the specific margins of a lesion, e.g., via fluoroscopy or some otherimaging procedure.

When used as a localization marker during a surgical procedure,ultrasound images of the radial-spoke marker 200 may be generated as aplurality of cross-sectional, two-dimensional views, e.g., on a display110. Identification of a location of the radial-spoke marker 200, aswell as its relative orientation, within the patient may be based on atrained set of ultrasound images of radial-spoke markers in differentorientations and cross-sectional views. In this way, the radial-spokemarker 200, which may be inserted with minimal intervention many days orweeks prior to a surgical procedure, may improve patient comfort andreduce challenges in surgical scheduling.

As should be appreciated, radial-spoke marker 200 is not limited to theparticular dimensions, materials, configurations and propertiesdescribed above.

FIG. 3 depicts an example biopsy site marker configured in amulti-layered spherical shape. As detailed above, current diagnosis andtreatment for breast cancer patients involve several steps. Initially,mammography or other forms of advance imaging may be used to determinewhether there are any abnormalities within a patient's breast(s). If so,an outpatient biopsy using image guidance is conducted to retrievespecimens of the site. During the biopsy procedure, a permanent implant(e.g., biopsy site marker) may be deployed to ‘mark’ the lesion that wasbiopsied. This permanent marker allows a physician to follow up, andpossibly a surgeon to resect (surgically remove) the tumor.Traditionally, a radiologist is needed prior to surgical removal toimage the breast using mammography and to place a wire in perpendicularorientation to the marker location. This wire remains in the patientthroughout that day until the surgery, at which time the surgeon followsthe metal wire and excises the marker and the lesion in an open surgery.

Following surgery, oral systemic chemotherapy may be delivered in orderto reduce any margins or lymph nodes where the cancer could have spread.Due to the sometimes harsh and systemic nature of the drugs, emphasishas been moving toward targeted drug delivery to the lesion site.However, current marking technologies are limited due to the materialsused, marker shape, size and ultimate detectability when visualizedunder advanced imaging (X-ray, MRI, ultrasound). Additionally, currentcommercial markers are passive landmarks and do not collect or transmitdata, nor are they able to respond to external stimuli. Furtherlimitations include, for example, the lack of marker distinctivenessthat prevents distinguishing markers from anatomical features andscarred tissue, as well as poor imaging characteristics of markerfabrication materials. Use of ultrasound as an imaging technology offersseveral benefits, including no radiation and low cost, ease of use, andbroad availability of technicians and machinery. Not only so, butultrasound imaging provides a better image of the lesion, lesion marginappearance and surrounding tissues. However, finding a marker underultrasound can be cumbersome. Metal markers tend to be very small andshow up hyperechoic under ultrasound, causing them to be confused withnatural features (e.g., such as air bubbles, calcifications, cooperligaments, etc.). While the crystallinity of these polymers (e.g., PLA,PGA, etc.) can be easily identified when compared to natural breasttissue, most polymer markers are resorbable and do not last very long invivo. The shape of some polymer markers presents as a long strand of‘rice-like’ bodies and may be confused with Cooper ligaments. Hydrogelpolymers, on the other hand, can be easily identified due to their watercontent, which is distinct and hypoechoic in nature (once fullyhydrated), but have the limitation of degradation and potential scarformation, which may appear malignant. Also, the appearance of thehydrated hydrogel could appear like a cyst or fibroadenoma (wider andshorter) with clear margins, there should be an internal feature thatcould aid in the differentiation from naturally occurring benignlesions. Ceramic materials may also be used for markers, but due totheir crystallinity and hard nature, they appear hyperechoic and tend tobe very small in size and do not have capability to change size orshape.

In sum, radiologists and surgeons would benefit if biopsy site markerscould be used as localization markers during surgery.Ultrasound-detectible markers may satisfy this currently-unmet need ashighly ergonomic, low cost, no radiation, readily available,non-invasive and patient friendly solutions. Similarly, providingsurgeons with a ‘wire-free’ option in which they could localizeintraoperatively the marker and the lesion, would enable easier accessand better surgical planes, leading to better surgical and cosmeticoutcomes.

A multi-layered marker may comprise a central core 310 enveloped byconcentric layers of one or more different materials. For example, themulti-layered marker 300 may be a multi-layered composite construct,made of biocompatible non-inflammatory polymers (could be synthetic oranimal derived) with the central core 310 of a permanent material(non-biodegradable, such as metal or ceramic, or a non-degradablepolymer such as nylon, PMMA, PEEK, PVP, PVA, etc.). The outer layers ofthe multi-layer construct may have a scaffold-like appearance with aseries of open and closed pores. The closed pores may be filled withair, saline, or a drug. These liquid- or gas-filled pores would serve asa vehicle to aid in localization of the multi-layered marker within thebreast tissue. The multi-layer construct may also be composed of aseries of biodegradable polymer layers (e.g., 1-500 nm in thickness),with different material properties than the scaffold layers or thecentral core, which may be deposited using a variety of thin filmassembly techniques. In aspects, each layer could contain a differentpercentage of porosity (e.g., closed pores filled with liquid or gas).This construct surrounds the permanent core material. The multi-layeredmarker 300 may be delivered minimally invasively during a biopsyprocedure using image guidance. The radiopaque permanent element (e.g.,central core 310) would be clearly distinguishable using X-ray, whilethe polymeric layers could be visualized under Ultrasound and/or MRI.

In aspects, the multi-layered marker 300 may remain in the patient'sbreast at the location of the biopsy site and will provide clear marginsand shape under ultrasound, with no posterior acoustic shadowing. If theresults of the biopsy are positive, at a follow up appointment, thesurgeon uses an ultrasound linear transducer (e.g., about 7-14 MHz) andplaces it on the breast. As soon as the surgeon starts scanning, themulti-layered marker 300 would be visible. That is, once the surgeonplaces the probe on the target for a few seconds (scanning back andforth), the internal content of the pores within the marker compositewill resonate, creating a detectable nonlinear echo response to theultrasound. Due to the content of the pores (e.g., gas or liquid), whenthe ultrasound acoustic waves hit the marker, the waves are not able tocontinue and bounce back. Moreover, the micro-sized acoustic responsemay cause layers to break or shed off of the outer layers. Such responsewould be seen by the user as ‘scattering’ as the original acoustic wavesare redirected due to the presence of rough surfaces (as layers breaksoff), which would be easily discernable from natural tissue and anatomyby the user. In this way, the user would be able to localize themulti-layered marker 300, including its depth and location.

Due to the nature of the multi-layered marker 300, multiple types ofpolymers may be deposited with different lengths of degradation (e.g.,from six months to one year or more). In this way, the multi-layeredmarker 300 would not be affected by the natural degradation andinflammatory response of the body to a foreign object. Also, as thedifferent layers can make a distinct echogenic profile, the marker canbe easily distinguished when each layer breaks off. Thus, themulti-layered marker 300 solves a critical need, which is thelocalization of the marker/biopsy site from three to six months afterbiopsy. For example, these multiple layers of different thicknessescould be shed off every time there is a follow up ultrasound scan, toaid in visualization. This is a critical time period, as mostchemotherapy regimens last between three to six months. During thisperiod, it would now be possible to gauge how well the chemotherapy isworking based ultrasound evaluation of the lesion site based on themarker. The fact the multi-layered marker 300 is easily seen underultrasound provides flexibility for the surgeon to localize the lesionwithout additional equipment (or help from advanced imagers), eitherintraoperatively in the operating room (OR).

The multi-layered marker 300 could also be used for targeted drugdelivery, as each layer could serve as a personalized cocktail ofchemotherapy drugs that could be released remotely and precisely. Inother aspects, the multi-layered marker 300 could be activated forlocalization using a remote activation. For instance, the permanent corecould be fabricated of a rare earth magnetic metal coated with layers ofpolymers. For later localization and activation, an external strongmagnet probe could be placed on the breast. When placed close to themarker, rare earth magnetic metal may extend its ‘length’ or change itsshape due to the magnetic field, causing the external polymer layers toeither break off or move elastically with the core. Such ‘movement’within the marker can be easily seen under ultrasound. However, use ofsuch magnetic metal materials would prevent the patient from being acandidate for MRI.

Although multi-layered markers 300A, 300B are illustrated as spheres, amulti-layered marker may be provided in any suitable shape or size. Forexample, the multi-layered marker may be in the shape of a square or anyother geometric shape. In aspects, one or more layers of themulti-layered marker may be composed of or comprise a chemotherapeuticdrug. Alternatively, one or more layers may be composed of or comprise acancer-cell binding agent. For example, firing ultrasound waves 306 maycause one or more layers (e.g., first layer 302 and/or second layer 304)of the multi-layered marker 300A to dissolve or break off, asillustrated by multi-layered marker 300B in which third layer 308 is nowan outer layer. When first layer 302 and/or second layer 304 arecomposed of a chemotherapeutic drug, treatment may be delivered directlyto a lesion in response to ultrasound waves. When first layer 302 and/orsecond layer 304 are composed of a cancer-cell binding agent exhibitingproperties capable of detection by different imaging modalities, aspecific margin or boundary of a lesion may be identified (e.g., viafluoroscopy or other imaging technique). In some aspects, first layer302 and second layer 304 may exhibit different properties such that thechemotherapeutic drug and/or cancer-cell binding agent is released atdifferent times or under different conditions. In other aspects, onelayer may comprise a chemotherapeutic drug while another layer maycomprise a cancer-cell binding agent, which layers may be activated atdifferent times or under different conditions.

Alternatively, first layer 302, or another layer such as second layer304 or third layer 308, may be composed of a material that is reactiveto changes in pH, temperature, electrolyte concentration, or othercondition of a bio-environment. For example, in response to changes inconditions, the material may fluoresce, become soluble and dissolve,exhibit changes in echogenicity, release a contrasting agent, or thelike. Tumor growth or progression may be evidenced by a reduction in pH(e.g., increased acidity), an increase in temperature (e.g., due toincreased cellular metabolism and/or vascularization), and/or a decreasein free calcium ions (e.g., due to an increase in Ca²⁺ uptake by cancercells) in surrounding tissues. In this case, a material that is reactiveto changes in pH, temperature and/or electrolyte concentration mayprovide an in-situ indication of a progression or regression of alesion.

In still other examples, one or more layers of the multi-layered marker300A and/or 300B may comprise or be composed of a rare earth magneticmetal, which may be activated by ultrasound waves or an external remotecontrol. For example, the rare earth magnetic metal may lengthen orshorten in response to activation. In this way, a shape of themulti-layered marker 300A and/or 300B may be altered upon activation ofthe rare earth magnetic metal. For instance, based on a change in shape,a multi-layered marker may be more readily detectable as a localizationmarker under ultrasound during a surgical procedure.

As should be appreciated, multi-layered marker 300A and/or 300B are notlimited to the particular dimensions, materials, configurations andproperties described above.

FIGS. 4A-4C depict an example biopsy site marker configured in anexpandable spherical lattice structure. Spherical lattice marker 400 maybe formed of Nitinol wire or some other shape-memory alloy or polymer.The Nitinol wire may be formed into a geodesic cage. In examples, theNitinol wire may form a two-dimensional geometric shape (e.g., pentagon,triangle, etc.) on facets or faces on the surface of the geodesic cage,e.g., pentagon facet 404 or triangle facet 406. In its condensed state(e.g., spherical lattice marker 400A), the wire edges of the geometricfacets may fold inward to create spikes 402. In some cases, the Nitinolwire may be configured into a first shape (e.g., an expandedconfiguration) under heated conditions and configured into a secondshape (e.g., a folded or condensed configuration) under cooledconditions. Although the spherical lattice marker 400 may be deliveredin the condensed configuration (e.g., second shape), it may “remember”the first shape and automatically deploy into the expanded configuration(e.g., spherical lattice marker 400B, 400C) based at least in part onthe shape-memory properties of Nitinol. Alternatively, the sphericallattice marker 400 may be configured with a wire or other actuator for“pulling” the spherical lattice marker 400 from a condensed state intoan expanded state after insertion at the biopsy site.

In some cases, the spherical lattice marker 400 may be delivered invarious sizes depending on a size of a target lesion. In this way, aprogression or regression of the lesion may be detected based on thesize of the marker as compared to the size of the lesion at the time ofa surgical or other procedure performed under ultrasound. When used as alocalization marker during a surgical procedure, ultrasound images ofthe spherical lattice marker 400 may be generated as a plurality ofcross-sectional, two-dimensional views, e.g., on a display 110.Identification of a location of the spherical lattice marker 400, aswell as its relative orientation, within the patient may be based on atrained set of ultrasound images of spherical lattice markers having thesame geometric facets in different orientations and cross-sectionalviews. In this way, the spherical lattice marker 400, which may beinserted with minimal intervention many days or weeks prior to asurgical procedure, may improve patient comfort and reduce challenges insurgical scheduling.

As should be appreciated, spherical lattice markers 400A-C are notlimited to the particular dimensions, materials, configurations andproperties described above.

FIG. 5 depicts an example biopsy site marker configured as a fibrouspolymer. Fibrous polymer marker 500 may be injected into a biopsy sitefollowing a biopsy procedure of a patient 112. In aspects, the fibrouspolymer marker 500 may be injected using an injection device 502 througha hollow tube or conduit 504 into tissues surrounding a lesion 506. Insome aspects, hollow tube 504 may be biodegradable and reabsorbed bypatient 112. For example, at the time of a biopsy, the resorbable tube504 could be placed after a core is removed, or could be pushed out fromthe distal end of the introducer at the site. The resorbable tube 504(e.g., about 2 cm in length) may remain at the biopsy site as a ‘placeholder’ and can be localized using ultrasound (as a distinct flathyperechoic structure, with a hollow hypoechoic core). Furthermore, theresorbable tube 504 may now serve as an introducer for delivering a‘sensing’ fiber (e.g., suitable for fibrous polymer marker 500), whichmay be less than about 1 millimeter in diameter. Such sensing fiber canbe used by the surgeon and/or a radiologist to minimally invasively mapout the biopsy site region. In this way, the sensing fiber may serve asa guiding system, which may shoot light or sound waves into the biopsycavity (e.g., where the biopsy core was removed), and it can capture theresponse from the surrounding tissue. For example, cancerous areaswithin the cavity wall may have different hardness or other propertiesthat reflect or absorb the emitted waves in different ways than normaltissue. The cancerous area can then act as a beacon, as hard cancerousareas have been known to have distinct elastic moduli (e.g., asdetermined by elastography). In some cases, the sensing fiber may beconnected to a computing system with a user interface for illustrating a‘heat’ map of the entire cavity as they fluoresce under a specificwavelength. An additional user interface could help with imaging the‘hot spots’ and could co-register or fuse with previous ultrasoundimages of FIG. 1C. This system could be used to minimally invasively mapout the cavity, and to confirm there are no remaining cancerous areas.The user interface could be co-registered with other imaging modalities(such as ultrasound or MRI), enabling the surgeon to understand wherethe ‘hot spots’ are relative to anatomical features. The sensing fibercould also be a vehicle for delivering drugs to the location of thelesion at the biopsy site. If light is used, then prior to inserting thefiber, the surgeon could inject a liquid agent designed to bind tospecific cancerous ‘biomarkers’ or cells. Thereafter, these spots couldbe visualized using near infrared (NIR) or fluorescence principles. Inthis case, a higher concentration of spots would imply that there is acancer left behind. In some cases, after resection, a similar resorbabletube could be placed. In this case, if there is a need for additionalsurgery (e.g., for cosmetic outcomes, implants, or addressing remainingmargins), a surgeon could use the post-resection resorbable tube to mapout remaining tissues and/or margins before performing the additionalprocedures.

The benefits of using a resorbable tube and/or sensing fiber may befar-reaching. For example, current intraoperative solutions use excisedex vivo tissue for imaging using different technologies, such as X-ray(which doesn't provide clear margins), OCT medical imaging, RamanSpectroscopy, Ultrasound, etc. However, all of these imaging modalitiesevaluate excised tissue outside of the body, so there are no (or verylimited) current in situ intraoperative solutions to detect remainingmargins within the cavity. Rather, surgeons must artificially evaluateand understand where the margins could be, as well as any additionaltissue that should be retrieved. Thus, benefits of the sensing fiberinclude minimally invasively delivery, e.g., after biopsy or resection,and in situ imaging, which could ultimately alter the way surgeries areplanned and carried out. The fiber placed in situ could overcome issueswith current external NIR probes that can only detect ‘targets’ within adepth of less than a couple of centimeters due to optical scatteringacross heterogeneous tissue planes.

In aspects, the fibrous polymer marker 500 may be comprised of anysuitable sensory fiber that is biocompatible and remains substantiallystable (e.g., insoluble) for a period of time within patient 112.Sensory fibers may include fibrous polymers that are reactive to light,heat, ultrasound waves, changes in pH, changes in electrolyteconcentration, and the like. For instance, fibrous marker 500 may detectan increase in temperature, e.g., due to increased cellular metabolismand/or increased vascularization, which may be indicative of aprogression of lesion 506. In contrast, fibrous polymer marker 500 maydetect a decrease in temperature, which may be indicative of aregression of lesion 506. In another example, fibrous marker 500 maydetect a decrease in pH and/or free calcium ion concentration in thevicinity of lesion 506, which may be indicative of a progression oflesion 506. Conversely, an increase in pH and/or free calcium ionconcentration may be indicative of a regression of lesion 506.

In response to detecting light, ultrasound waves, changes intemperature, changes in pH, changes in electrolyte concentration, andthe like, the structure or properties of the fibrous polymer marker 500may be altered. For instance, portions of fibrous polymer marker 500that detect such conditions may fluoresce, thicken, emit visible light,emit heat, crystalize, increase echogenicity, or otherwise be altered instructure or properties, as illustrated by altered fibrous material508B. In contrast, other portions of fibrous polymer marker 500 that donot detect such conditions may remain unaltered, as illustrated byunaltered fibrous material 508A. When the altered fibrous material emitsheat in response to detecting changes in the micro-environmentsurrounding lesion 506, infrared thermography (IRT) or thermal imagingmay be used to visualize a heat map produced by the altered fibrousmaterial in the vicinity of lesion 506. In this way, changes in themargin of lesion 506 may be mapped or outlined, new masses may beidentified, changes in the bio-environment (e.g., changes in pH,temperature, or electrolyte concentration) surrounding the lesion 506may be detected, and the like. Similarly, other imaging techniques maybe utilized to detect other alterations of the fibrous material, e.g.,ultrasonic imaging, magnetic resonance imaging, etc. Suitable sensoryfibers may include but are not limited to: aramid fiber,aramid-polymethylmethacrylate (aramid-PMMA), high modulus carbon fiber,hydrogel-based optical fiber, fiberglass, and the like.

As should be appreciated, fibrous polymer marker 500 is not limited tothe particular dimensions, materials, configurations and propertiesdescribed above.

FIG. 6 depicts an example method 600 for determining informationregarding a lesion from an implanted marker. The operations of method600 and the other methods discussed herein may be performed by at leastone processor in conjunction with other components of a suitableoperating environment, such as the operating environment 150 in FIG. 1E,within a system such as system 100 depicted in FIGS. 1A-1D.

As detailed above, a biopsy site marker may be implanted at or near alesion prior to a surgical procedure. For instance, at operation 602,e.g., during a biopsy procedure, the biopsy site marker may be implantedinto a patient near a suspicious lesion. As described above, theimplanted marker may be configured with special features or propertiesfor delivering drugs or treatments and/or monitoring a progression orregression of the lesion. Moreover, the implanted marker may bedetectable as a localization marker during a surgical proceduresubsequent to the biopsy procedure. In this way, the implanted markermay not merely serve as a landmark for future examination of the lesion,but may be configured to monitor or treat the lesion as well as serve asa localization marker during a subsequent surgical procedure. Thus, theimplanted marker may not only minimize intrusion of the patient, butprovide on-going benefits with regard to the treatment, diagnostics andlocalization of the lesion.

At optional operation 604, the implanted marker may be activated. Theimplanted marker may be activated in any of a number of ways. Forinstance, the implanted marker may be activated by ultrasound waves, aningested agent, or an external remote. Alternatively, the implantedmarker may be activated (or reactive) to changes in conditions in abio-environment of the lesion. For instance, the implanted marker mayreact or be responsive to changes in pH, changes in temperature, changesin electrolyte concentration, and the like. In response to activation,the structure of the implanted marker may be altered (e.g., bythickening, folding, expanding, dissolving, lengthening or shortening,and the like) or the properties of the implanted marker may be altered(e.g., by emitting heat, emitting visible light, increasing ordecreasing echogenicity, vibrating, increasing or decreasing solubility,fluorescing, releasing a drug or agent, and the like). In some cases, inresponse to activation, the implanted marker may send or receivemonitored data (e.g., via a transceiver) to or from an external device.

At operation 606, data may be received from the implanted device. Insome cases, the data may be received by performing imaging or some othertechnique to gather data from the implanted marker. For instance, one ormore of ultrasound imaging, MRI, X-ray imaging, thermography,elastography, fluoroscopy, and the like, may be performed to gather dataassociated with the implanted marker's location, orientation, propertiesor structure. Alternatively, the implanted marker may actively send datato an external device. For instance, in the case of an implanted chip,the implanted marker may send monitored data regarding the lesion (e.g.,such as temperature data, pH data, electrolyte concentration data, bloodflow or pressure data, and the like).

At operation 608, the received data may be analyzed. For instance, datagathered by imaging or other technique may be analyzed to detect changesin the structure or properties of the implanted marker, such as size,shape, echogenicity, luminosity or fluorescence, heat, and the like.Based on the composition of the implanted marker, such changes instructure or properties may be indicative of changes in abio-environment surrounding the implanted marker, such as changes intemperature, pH, electrolyte concentration, etc. Additionally oralternatively, using ultrasound or other imaging modality, a location ororientation of the implanted marker may be determined, as describedabove with reference to FIGS. 1A-1D. Still further, raw data receivedfrom an implanted chip or sensor associated with the implanted markermay be processed and analyzed. When processed, the raw sensor data mayprovide information regarding a bio-environment surrounding theimplanted marker, such as temperature, pH, electrolyte concentration,blood flow, blood pressure, etc.

At operation 610, information regarding the lesion may be determinedfrom the analyzed data. For instance, if the analyzed data is indicativeof an increase in temperature in the bio-environment surrounding theimplanted marker, it may be determined that the lesion is progressing orgrowing. Similarly, if the analyzed data is indicative of a decreasingin pH and/or free calcium ion concentration in the bio-environmentsurrounding the implanted marker, it may be determined that the lesionis progressing or growing. Conversely, if the analyzed data isindicative of a decrease in temperature or an increase in pH and/or freecalcium ion concentration, in the bio-environment surrounding theimplanted marker, it may be determined that the lesion is regressing orshrinking. Additionally or alternatively, if the analyzed data isindicative of a margin of the lesion (e.g., via ultrasound imaging,thermography, fluoroscopy, etc.), the determined margin may be comparedto previous margin information to determine whether the lesion isprogressing or regressing. In still other examples, a relative size ofthe implanted marker may be compared to a size of the lesion (e.g.,based on margin data as described above). When a size of the implantedmarker is indicative of an initial or baseline size of the lesion, thedetermined relative size of the implanted marker based on the analyzeddata may be used to determine whether the lesion has progressed orregressed. As should be appreciated, additional information regardingthe lesion may be determined from analyzing data associated with theimplanted marker, as described throughout the present disclosure.

At operation 612, the determined information regarding the lesion may bedisplayed on a display device. For instance, the determined informationmay be in the form of a report, one or more images, etc. In some cases,a notification of the determined information may be forwarded to medicalpersonnel and/or the patient.

FIG. 7A depicts an example method 700 for localization of a lesion orimplanted marker. As detailed above, the marker may have been implantedat or near the lesion prior to a surgical procedure. For instance, whenthe lesion was detected in a patent, the marker may have been implantedduring a biopsy procedure. In this way, rather than requiringcoordination and placement of a localization wire at the time ofsurgery, the previously-implanted marker may be utilized to localize thelesion during the surgical procedure. Thus, logistics and scheduling onthe day of surgery are simplified, as well as reducing an overallsurgical time for the patient. Further benefits are realized because theimplanted marker may be specially designed for detection usingultrasound or other imaging technologies to provide live imaging andlesion location data during the surgical procedure. The operations ofmethod 700 and the other methods discussed herein may be performed by atleast one processor in conjunction with other components of a suitableoperating environment, such as the operating environment 150 in FIG. 1E,within a system such as system 100 depicted in FIGS. 1A-1B.

At operation 702 an array of ultrasonic sound waves are emitted from anultrasonic transducer of an ultrasound probe. The ultrasound waves enterthe interior of the patient and are reflected from the components of theinterior of the patient, including natural tissue as well as theimplanted marker, as discussed above. The reflected ultrasonic waves arethen detected at operation 704. At operation 706, ultrasound image datais then generated from the detected reflected ultrasonic sound waves.The ultrasound image data may be B-mode ultrasound imaging data.

At operation 708, the image data is analyzed by a processor of theultrasound localization system to identify or detect the implantedmarker within the image data. As discussed above, the image analysistechniques may be based on image processing techniques, and machinelearning techniques, such as neural networks, deep learning algorithms,or other pattern matching techniques, that are trained based on theshape of the marker implanted in the patient. As an example, where theshape of the marker has a unique cross-section in 360 degrees ofrotation, the image analysis algorithms may first be trained on a set ofultrasound images containing a cube-shaped marker in differentorientations and cross-sectional views. A current ultrasound image orimage data is then provided as an input into the trained image analysisalgorithms to detect or identify the marker. Identifying the marker maygenerally be based on the cross-section of the marker as the ultrasoundimage is a two-dimensional image.

Identifying the marker may also include identifying a particularcross-section of the marker in order to determine an orientation of themarker. For instance, the orientation of the marker can be determinedwhen the marker is detected in at least two different sections based ondifferent viewing angles, such as cube or a rectangular prism. If themarker has symmetry in 360 degrees of rotation, determining anorientation from ultrasound imaging alone is more difficult. In someexamples, the marker may be identified by a user, such as an ultrasoundtechnician, on a display of an ultrasound image. Such an identificationmay be provided as an input into the ultrasound system (e.g., a click ofa pointer on the display) to allow for a distance to the marker to bedetermined. For instance, the distance may be determined based on thenumber of pixels between the two objects in the image.

If the marker is detected or identified in operation 708, an ultrasoundimage may be displayed that highlights or otherwise emphasizes themarker. In some examples, the marker is highlighted with a particularcolor, having its brightness increased, or otherwise causing the markerto be highlighted. The marker may also be outlined with an artificialoutline to emphasize the presence of the marker. A graphical indicatormay also be displayed on top of or proximate the marker. For example, anarrow may be displayed in the ultrasound image pointing to the marker.The color of the marker may also be changed to further highlight oremphasize the marker from the remainder of the ultrasound image. Thehighlighting or emphasis of the ultrasound may be accomplished bymodifying the ultrasound image itself or adding a layer on top of theultrasound image to achieve the desired highlighting or emphasis of themarker.

Other indicators may also be triggered when the marker is identified andin the field of view. For instance, an audible sound, such as beep, maybe emitted when the marker comes within a field view. In some examples,a tone having a varying frequency or intensity may also be emitted basedon how close the marker is to the center of the field of view. Lights ofother visual indicators may also be displayed when the marker comes intothe field of view. Haptics on the ultrasound probe may also be activatedwhen the marker comes into the field of view.

At optional operation 710, signals from the various localizationtransceivers are processed by at least one of the processors in theultrasound localization system. As discussed above, the ultrasoundlocalization system may include at least a probe localizationtransceiver, a marker localization receiver, and/or an instrumentlocalization transceiver. Those transceivers emit signals providinglocalization information for the device to which they are attached orincorporated, e.g., the ultrasound probe, the marker, and/or theincision instrument. The signal(s) emitted by the transceiver(s) may beprocessed to determine the orientation or location of the ultrasoundprobe, the marker, and/or the incision instrument at operation 712. Theorientation may also be determined from the cross-section of the markerand/or the incision instrument in the ultrasound image. The orientationand location of those devices may be determined or provided relative toother items, such as the incision instrument, the marker, the ultrasoundprobe, a magnetic direction, a normal to gravity, etc. With theorientation and location of the devices, additional information can begenerated and provided to the surgeon to assist in guiding the surgeonto a lesion within the patient. For example, the orientation informationcan assist the surgeon in determining if an incision instrument isaligned with a particular axis of the marker and/or a boundary of thelesion.

At operation 714, a distance to the lesion and/or the identified markeris determined. For instance, the distance may be determined by at leastone processor, such as processor 152 in operating environment 150discussed above. The determination may be based on the identification ofthe marker and the data available from the detected reflected ultrasonicsound waves. The determined distance may be at least one of a distancefrom a portion of the ultrasound probe to the at least one of the markeror the lesion, a distance from a portion of a scalpel to the at leastone of the marker or the lesion, or a distance from a portion, such asthe tip, of an incision instrument to the at least one of the marker orthe lesion. In determining the distance from the ultrasound probe to themarker, a calculation is performed based on the speed of sound based onthe tissues through which the ultrasonic sound waves passed. Forexample, the speed of sound is known for the various tissues in thehuman body, and a distance calculation can be performed based on thetravel time of the ultrasonic sound waves. Identification of theorientation of various devices in the ultrasound localization systemalso allows for the location to be determined in three-dimensional spaceand the determined distance may include a directional component, such asa vector.

In some examples, a portion of the incision instrument, such as the tipof the incision instrument, can be identified in the ultrasound imagedata. The distance to the incision instrument from the ultrasound probecan be determined from the detected reflected ultrasonic sound waves ina similar manner as determining the distance to the marker. Based on thedistance from the ultrasound probe to the marker and the distance fromthe ultrasound probe to the incision instrument, a distance from themarker to the incision instrument may also be determined. In someexamples, the determination can be made using trigonometry principalssuch as laws of cosines. One example of the method of determining thedistance to the marker is shown in FIG. 7B. In the figure, the distancefrom the ultrasound probe 102 to the marker 116 is shown as “a,” thedistance between the marker 116 and the incision instrument 126 is shownas “b”, and the distance from the ultrasound probe 102 to the incisioninstrument 126 is shown as distance “c.” The relationships between thedistances may be represented as a²+b²=c². Accordingly, with two of thedistances being determined from ultrasound depth calculations and/orlateral distance measurements from an ultrasound image, the otherdistance may be determined. Similarly, where one of the distances andone or more internal angles are determined, the other distances may alsobe determined through the use of trigonometric principles.

Determining the distance to the edge of a lesion may be based on thedistance to the marker as well as the orientation of the marker. Asdiscussed above, the orientation of the marker may be determined fromthe cross-section of the marker. For example, at the time the marker isinserted into the patient, the relative size and shape of the lesion mayalso be determined through various imaging techniques, includingultrasound, mammography, tomography, etc. When the marker is inserted, arepresentation of the edge of the lesion may be generated relative tothe location and orientation of the marker. For instance, the edge ofthe lesion may be represented as a function of the location andorientation of the marker. Thus, when the distance and orientation ofthe marker are determined, the distance to the edge of a lesion may alsobe determined.

Once the distance to the lesion or the marker is determined by theprocessor of the ultrasound localization system, at operation 716, thedetermined distance is displayed on the display the operativelyconnected to the processor. For example, the distance may be displayedin a user interface element on the display. Other techniques fordisplaying or otherwise providing an indication of the determineddistance are also possible, such as a dedicated indicator or an audibleindicator. In other examples, the distance may be displayed or indicatedon the ultrasound probe or the incision instrument.

Distances to the lesion or marker may be determined from multipleorientations as well. Determining the distance to the lesion or markerin multiple orientations may further define the location of the markeror lesion in three-dimensional space. The ultrasound system can usesoftware beam forming techniques to lock on to the shape of the markerbased on the fact that the marker is the same shape from two separatepositions, in examples where the marker has such a geometry. Other imageanalysis techniques as discussed above may be used to identify themarker and lock on to the marker during imaging.

FIG. 8A depicts an example method 800A for localization and navigationto an implanted marker. As detailed above, the marker may have beenimplanted at or near the lesion sometime prior to a surgical procedure.For instance, when the lesion was detected in a patent, the marker mayhave been implanted during a biopsy procedure. Thereafter, even monthslater, the marker may be used for localization during treatment orexamination. In this way, rather than requiring coordination andplacement of a localization wire at the time of surgery, thepreviously-implanted marker may be utilized to localize the lesionduring the surgical procedure. Thus, logistics and scheduling on the dayof surgery are simplified, as well as reducing an overall surgical timefor the patient. Further benefits are realized because the implantedmarker may be specially designed for detection using ultrasound or otherimaging technologies to provide live imaging and lesion location dataduring the surgical procedure.

At operation 802, an array of ultrasonic sound waves are emitted from anultrasonic transducer of an ultrasound probe at a first position. Theultrasound waves enter the interior of the patient and are reflectedfrom the components of the interior of the patient, including naturaltissue as well as the implanted marker, as discussed above. Thereflected ultrasonic waves are then detected at the first position, atoperation 804. At operation 806, ultrasound image data is then generatedfrom the detected reflected ultrasonic sound waves at the first positionof the ultrasound probe.

At operation 808, the image data is analyzed by a processor of theultrasound localization system to identify or detect the implantedmarker within the image data, using any of the techniques discussedabove. In some examples, an ultrasound image may also be displayedshowing the identified marker. In such examples, the marker may behighlighted or otherwise emphasized using any of the techniquesdescribed above.

Other indicators may also be triggered when the marker is identified andin the field of view. For instance, an audible sound, such as beep, maybe emitted when the marker comes within a field view. In some examples,a tone having a varying frequency or intensity may also be emitted basedon how close the marker is to the center of the field of view. Lights ofother visual indicators may also be displayed when the marker comes intothe field of view. Haptics on the ultrasound probe may also be activatedwhen the marker comes into the field of view.

In some examples, signals from the various localization transceivers areprocessed by at least one of the processors in the ultrasoundlocalization system to determine orientation and/or localizationinformation for the ultrasound probe, the marker, and/or the incisioninstrument. Any of the techniques described above may be utilized forprocessing the signals and using the resultant information. Forinstance, a distance to the marker or the edge of the lesion may bedetermined and displayed, as discussed above.

In some cases, the ultrasound technician may move the ultrasound probefrom the first position to a second position. The second position maydiffer from the first position in orientation of the ultrasound probe,location of the ultrasound probe, or both. With the ultrasound probe inthe second position, at operation 810, an array of ultrasonic soundwaves are emitted from the ultrasonic transducer of the ultrasound probeat a second position. The ultrasound waves enter the interior of thepatient and are reflected from the components of the interior of thepatient. The reflected ultrasonic waves are then detected at the secondposition, at operation 812. At operation 812, ultrasound image data isthen generated from the detected reflected ultrasonic sound waves at thesecond position of the ultrasound probe.

At operation 814, the image data is analyzed by a processor of theultrasound localization system to attempt to detect the implanted markerwithin the image data, using any of the techniques discussed above. Atoperation 814, however, the image analysis techniques fail to locate themarker within the image data from the second position because the markeris not within the field of the view of the ultrasound probe in thesecond position.

Based on the marker not being detected in operation 816, a navigationindicator is generated at operation 818. As discussed above, thenavigation indicator provides navigation guidance for the ultrasoundtechnician to find the marker. The navigation indicator may be based onthe ultrasound identification of the marker when the ultrasound probewas in the first position. For example, the location and orientation ofthe ultrasound probe may be tracked or recorded from the first positionto the second position. As such, providing guidance to return to aposition where the marker can be seen and identified, e.g., a positionwhere the marker is within the field of view, is possible. In otherexamples, the signals from the various localization transceivers may beused to determine the location of the marker and generate the navigationindicator. As discussed above, the ultrasound localization system mayinclude at least a probe localization transceiver, a marker localizationreceiver, and/or an instrument localization transceiver. Thosetransceivers emit signals providing localization information for thedevice to which they are attached or incorporated, e.g., the ultrasoundprobe, the marker, and/or the incision instrument. The signal(s) emittedby the transceiver(s) may be processed to determine the orientation orlocation of the ultrasound probe, the marker, and/or the incisioninstrument. The orientation and location of those devices be determinedor provided relative to other items, such as the incision instrument,the marker, the ultrasound probe, a magnetic direction, a normal togravity, etc. With the orientation and location of the devices,additional information can be generated and provided to the surgeon toassist in guiding the surgeon to a lesion within the patient. Forexample, when the orientation and location information of the ultrasoundprobe and the marker are known, directional information may bedetermined to position the ultrasound probe to bring the marker into thefield of the view of the ultrasound probe.

At operation 820, the navigation indicator is displayed. Displaying thenavigation indicator at operation 820 may include illuminating anindicator on a display or creating a graphical user interface element todirect the ultrasound technician to bring the marker into the field ofview of the ultrasound probe. For instance, the navigation indicator mayinclude a series of arrows. Individual arrows may be highlighted todirect the ultrasound technician to move the ultrasound probe in aparticular direction, as described above. Other types of navigationindicators may also be utilized to provide guidance to the ultrasoundtechnician to find the marker. For example, indicators may also beprovided in the ultrasound probe itself to assist the technician inbring the marker into the field of view.

FIG. 8B depicts another example method 800B for localization andnavigation to an implanted marker. Method 800B provides for a continuousultrasound imaging method that allows an ultrasound technician tocontinuously image a patient with the ultrasound probe and continue toreceive feedback regarding the location of the marker and/or the lesion.At operation 850, an array of ultrasonic sound waves are emitted from anultrasonic transducer of an ultrasound probe. The ultrasound waves enterthe interior of the patient and are reflected from the components of theinterior of the patient, as discussed above. The reflected ultrasonicwaves are then detected at operation 852.

At operation 854, based on the reflected ultrasonic sound waves that aredetected at operation 852, ultrasound image data is then generated andanalyzed. Any of the image analysis techniques discussed above may beused. Based on the analysis of the image data at operation 854, adetermination is made at operation 856 as to whether the marker has beenidentified or detected and is thus present in the ultrasound image data.

If the marker is determined to be present in the ultrasound image dataat operation 856, the method 800B proceeds to operation 858 where themarker is highlighted or otherwise emphasized in an ultrasound imageusing any of the techniques described above. At operation 860, adistance to the marker and/or the lesion may also be determined anddisplayed using any of the techniques described above. The method 800Bthen flows back to operation 850 and method 800B repeats.

If the marker is determined not to be present in the ultrasound imagedata at operation 856, the method 800B proceeds to operation 862 wherethe marker location is determined. The location of the marker may bedetermined based on a prior identification of the marker in anultrasound image and/or orientation and location information derivedfrom signals from any of the localization transceivers, using any of thetechniques described above. The determined location of the marker isthen used to generate and display a navigation indicator at operation864, using any of the techniques described above. From operation 864,the method 800B then flows back to operation 850 and method 800Brepeats.

FIG. 9 depicts an example method 900 for localization and detection ofan implanted marker and an incision tool. Method 900, or any subset ofoperations in method 900, may be used in combination and/or conjunctionwith any of the other methods discussed above. At operation 902, inputregarding a type of marker is received from a user, such as anultrasound technician. The input may be received from a user interfacepresented on the same display used for displaying the ultrasound image.For example, input may be provided indicating the type of marker thathas been implanted in the patient. The input may indicate the shape andsize of the marker. In an example, the input may include providing amodel number or other identifying information for the marker. Based onthe input, the dimensions and other information about the marker may beobtained, such as from a local or remote database storing suchinformation. The dimensions of the marker may then be used by the imageanalysis techniques to assist in identification of the marker within theultrasound image. At operation 904, based on the input regarding themarker type, the ultrasound image data is analyzed using image analysistechniques to identify the marker.

At operation 906, input regarding a type of incision tool is receivedfrom a user, such as an ultrasound technician. The input may be receivedfrom a user interface presented on the same display used for displayingthe ultrasound image. The user interface may be the same user interfaceas the user interface used for gathering information on the type ofmarker. The input may be provided indicating the type of incisioninstrument that is being used with the patient. The input may indicatethe shape and size of the incision tool or a portion of the incisiontool. For example, the input may indicate the size and shape of the tipof a particular incision tool such as a scalpel. In an example, theinput may include providing a model number or other identifyinginformation for the incision instrument. Based on the input, thedimensions and other information about the incision instrument may beobtained, such as from a local or remote database storing suchinformation. The dimensions of the incision instrument may then be usedby the image analysis techniques to assist in identification of theincision instrument within the ultrasound image. At operation 906, basedon the input regarding the incision instrument type, the ultrasoundimage data is analyzed using image analysis techniques to identify theincision instrument.

Once the marker and the incision instrument have been identified, adistance to the marker, the lesion, and/or the incision instrument maybe determined at operation 910. The determined distance may be any ofthe determined distances discussed above and may utilize any of thetechniques discussed above. As an example, the distance from the tip ofthe incision instrument to the marker may be determined from theultrasound image. For instance, once the incision instrument isidentified in the ultrasound image and the marker has been identified inthe same image, the distance can be determined by measuring the distancebetween the two identified objects. The determination of the distancemay be determined automatically by a processor in combination with theidentification of the objects. The determination of the distance mayalso be done based on user input. For example, with the marker andincision instrument highlighted, or otherwise visually distinguished, onthe ultrasound image, input can be provided to draw a line between themarker and the incision instrument. The length of the line may then bedetermined by the processor of the operating environment. Once thedistance has been determined, the distance is displayed at operation912.

FIG. 10A depicts an example system 1000 for imaging a specimen 117. Oncea lesion 114 is removed during a surgical procedure, such as alumpectomy, a surgeon may image the specimen 113 containing the lesion114 to confirm that the margin of healthy tissue surrounds the lesion114. Such an analysis of the margins helps ensure that all the abnormaltissue, such as cancerous tissue, has been removed from the region ofinterest of the patient. If the margins are not such that the surgeonfeels confident that all the cancerous tissue has been removed, thesurgeon returns to surgery to remove additional tissue. Current systemsfor imaging specimens, however, generally rely on x-ray exposures. Thesex-ray systems can take up significant space and are costly. The presenttechnology provides an ultrasound-based solution that is able to bothreduce the cost and footprint for imaging margins of a specimen removedfrom a patient during a surgical procedure. The use of the ultrasoundtechnology allows for a quick imaging procedure and thus a quickermargin confirmation process. The ultrasound imaging procedure may alsooccur directly in the operating room. These benefits allow for shorterdurations of surgeries.

To perform the imaging and margin confirmation, the specimen 113 isplaced on a surface 117. An ultrasound probe 102 is placed on thespecimen 113 to image the specimen 113. In the example illustrated, thespecimen is spherically shaped for exemplary purposes. The theoretical,predicted, or ideal specimen location 115 (shown in dashed lines) islocated at the center of the specimen 113. That predicted location 115may be the location of where the surgeon believed the lesion 114 shouldbe within the specimen. The predicted location 115 may be based on wherethe marker was located within the patient. In some examples, the markeris located in the specimen 113 at the location of the predictedlocation. The predicted location 115 is used for purposes of calculationto determine whether the margins of the specimen are sufficient. Thedistance to the predicted location 115 may be represented as a distanceX from the top of the specimen to the center of the predicted location115 and a distance Y from the center of the predicted location 115 tothe surface 117. The distances X and Y represent the location of thepredicted location 115. Where the predicted location 115 is in thecenter of the specimen 113, the distance X will be equal to distance Y.

The actual location of the lesion 114, however, may not be at thepredicted location 115, as depicted in FIG. 10A. The ultrasound probe102 is used to determine the actual location of the lesion 114 withinthe specimen 113. Through the distance measuring techniques ofultrasound technology discussed above, a distance A to the center of thelesion 114 from the ultrasound probe 102 and a distance B from thecenter of the lesion 114 to the surface 117 may be determined. In theexample where the predicted location 115 was in the center of thespecimen 113, if the difference between the distance A and the distanceB is non-zero, the margin of the specimen 113 is not symmetric and theactual location of the lesion 114 is different from the predictedlocation 115. If the difference between the distance A and the distanceB is greater than a predetermined threshold, the margins may be deemedinsufficient and the surgeon may have to return to surgery to removeadditional tissue. In addition, the difference between the distance Aand the distance X may be determined, and if that difference exceeds apredetermined threshold, then the margins may be deemed insufficient.Similarly, the difference between the distance B and the distance Y maybe determined, and if that difference exceeds a predetermined threshold,the margins may be deemed insufficient.

As a reference frame for the system 1000 depicted in FIG. 10A, they-axis extends vertically through the image, the x-axis extendshorizontally across the image, and the z-axis extends into the image.Accordingly, the distances X and Y and A and B are measured along theY-axis in the example depicted in FIG. 10A.

To measure or determine additional margins from different orientations,the probe 102 or the specimen 113 may be rotated. FIG. 10B depicts theultrasound system 1000 of FIG. 10A with the specimen rotated around thez-axis by 90 degrees. The distance to the center of the predictedlocation 115 from the probe 102 in this orientation is represented bythe distance V and the distance from the center of the predictedlocation 115 to the edge of surface is represented by the distance W.Similar to the measurements in the prior orientation, marginverifications can be performed based on the differences between therespective distances. For instance, in the example where the predictedlocation 115 was in the center of the specimen 113, if the differencebetween the distance C and the distance D is non-zero, the margin of thespecimen 113 is not symmetric and the actual location of the lesion 114is different from the predicted location 115. If the difference betweenthe distance C and the distance D is greater than a predeterminedthreshold, the margins may be deemed insufficient and the surgeon mayhave to return to surgery to remove additional tissue. In addition, thedifference between the distance C and the distance V may be determined,and if that difference exceeds a predetermined threshold, then themargins may be deemed insufficient. Similarly, the difference betweenthe distance D and the distance W may be determined, and if thatdifference exceeds a predetermined threshold, the margins may be deemedinsufficient.

FIG. 10C depicts the ultrasound system 1000 of FIG. 10A with theultrasound probe rotated such that it oriented along the x-axis ratherthan the rotating the specimen. The same distances may be measured aswere measured in the configuration of the specimen 113 and the probe 102depicted in FIG. 10B. For instance, the distance to the center of thepredicted location 115 from the probe 102 along the x-axis isrepresented by the distance V and the distance from the center of thepredicted location 115 to the edge of the specimen 113 opposite theprobe is represented by the distance W. In some implementations,rotating the specimen 113 may be favored over rotating the ultrasoundprobe 102 due the reflections of ultrasound waves off of the surface117. Such reflections may make distance measurements from the probe tothe edge of the specimen 113 on the surface 117 easier to determine.

While effectively only two different relative orientations have beendepicted, the probe 102 or the specimen 113 may be rotated to measurefrom any additional orientations. For instance, the probe 102 may berotated to be aligned with the z-axis, and measurements of the specimen113 and lesion 114 may be measured along the z-axis. With the distancesto the lesion measured along three planes, such as along the x-axis,y-axis, and z-axis, the location of the lesion in three-dimensionalspace can be determined. Thus, the margins of the lesion 114 within thespecimen 113 may be determined.

In addition, distances from the exterior of the specimen 113 to the edgeof the lesion 114 may be directly measured with use of the ultrasoundprobe 102. That is, the actual margin between the edge of the lesion 114and the edge of the specimen 113 may be directly measured. The specimen113 may be imaged at as many orientations as desired to determinewhether the actual margins satisfy the desired or predetermined margins.For example, if a surgeon desires that the margins on all sides of thelesion 114 be greater than millimeters, the ultrasound system 1000 maymeasure the margins to verify that such margins are present in thespecimen 113. In some examples, the measurement and verification may beautomated by the ultrasound system 1000. For example, as the ultrasoundprobe 102 moves around the specimen 113, measurements of the margins ateach orientation may be measured. If at any point the margin is lessthan the desired, required, or predetermined margin (e.g., 5 mm), analert or alarm may be generated. The alert along with the location andorientation of the probe relative to the specimen may be recorded anddisplayed or incorporated into a report. As such, a full scan of thespecimen may be completed at each occurrence of a margin being less thanthe desired margin may be recorded and reported or displayed. Thesurgeon may then access the report or display to determine in whichdirections additional tissue needs to be removed from the patient.

It is also contemplated within the scope of this disclosure that thespecimen is placed in a container and placed on a table. The geometriesof the container are subtracted from the specimen geometries and thedepth of the marker is calculated. It is also contemplated within thescope of the disclosure that the calculations shown above can apply toother geometries of the specimen. The specimen can be any shape and morecomplex calculations can be performed to determine the distances to thecenter of the marker or lesion and the specimen. The different shapes ofthe specimen can be stored in the ultrasound system and automaticallymatched to a particular profile to help facilitate the calculations andmargin determinations.

FIG. 11 depicts a method 1100 for confirming margins of a specimen. Atoperation 1102, a specimen containing a lesion is imaged in a firstorientation using an ultrasound probe. The first orientation may bealong a particular axis, such as the y-axis. Imaging the specimen mayinclude emitting an array of ultrasonic sound waves from an ultrasonictransducer of the ultrasound probe. The ultrasound waves enter theinterior of the specimen and are reflected from the components of theinterior of the specimen, similar to how the ultrasonic sound wavesinteract with the interior of the patient as discussed above. Thereflected ultrasonic waves are then detected, and based on the reflectedultrasonic sound waves ultrasound image data is then generated that canbe analyzed. At operation 1104, based on the imaging of the lesion atoperation 1102, the location of the lesion in the first orientation maybe determined. Determining the location of the lesion may includedetermining distances to the center of the lesion from the probe and/orthe distance from the center of the lesion to the surface, such asdistance A and distance B discussed above with reference to FIG. 10A.Determining the location of the lesion may also include determiningwhether one or more margins in the first orientation are within anacceptable range or greater than the desired margins of the surgeon.Such a determination may be made by a direct measurement of distancefrom the probe to the edge of the lesion and then comparing thatmeasurement to the desired margin. The determination may also bedetermined by comparing the location of the lesion in the firstorientation with a predicted location of a lesion, as discussed abovewith reference to FIG. 10A. If the determined margins of the specimenare below the desired margins, an alert may be generated at operation1106. The alert may be audible or visual. For instance, an alertindicating the margin at the current orientation is too small. The alertmay also be recorded or otherwise reported to the surgeon along withdetails of the current orientation so that the surgeon is able todetermine where additional tissue needs to be removed from the patient.

At operation 1108, the specimen is imaged at a second orientation, suchas along the x-axis. Imaging the specimen at the second orientation mayinvolve rotating the specimen to the second orientation or rotating theprobe to the second orientation. At operation 1110, based on the imagingof the lesion at operation 1108, the location of the lesion in thesecond orientation may be determined. Determining the location of thelesion may include determining distances to the center of the lesionfrom the probe and/or the distance from the center of the lesion to thesurface, such as distance C and distance D discussed above withreference to FIGS. 10B-10C. Determining the location of the lesion mayalso include determining whether one or more margins in the firstorientation are within an acceptable range or greater than the desiredmargins of the surgeon. Such a determination may be made by a directmeasurement of distance from the probe to the edge of the lesion andthen comparing that measurement to the desired margin. The determinationmay also be determined by comparing the location of the lesion in thesecond orientation with a predicted location of a lesion, as discussedabove with reference to FIG. 10B. If the determined margins of thespecimen are below the desired margins, an alert may be generated atoperation 1112. The alert may be substantially the same as the alertgenerated in operation 1106 but for the second orientation.

At operation 1114, the specimen is imaged at a third orientation, suchas along the z-axis. Imaging the specimen at the third orientation mayinvolve rotating the specimen to the third orientation or rotating theprobe to the third orientation. At operation 1116, based on the imagingof the lesion at operation 1114, the location of the lesion in the thirdorientation may be determined. Determining the location of the lesionand the margins for the specimen may be similar to the techniquesdiscussed above, but for the third orientation. If the determinedmargins of the specimen are below the desired margins, an alert may begenerated at operation 1118. The alert may be substantially the same asthe alert generated in operations 1106 and 1112 but for the secondorientation. Method 1000 may then repeat for additional orientationsbeyond the first three orientations. For instance, the specimen may becontinuously imaged at a variety of angles or orientations. At eachorientation, a margin determination may be made and reported.

As should be appreciated, the operations described in the above methodsare described for purposes of illustrating the present methods andsystems and are not intended to limit the disclosure to a particularsequence of steps, e.g., steps may be performed in differing order,additional steps may be performed, and disclosed steps may be excludedwithout departing from the present disclosure.

The embodiments described herein may be employed using software,hardware, or a combination of software and hardware to implement andperform the systems and methods disclosed herein. Although specificdevices have been recited throughout the disclosure as performingspecific functions, one of skill in the art will appreciate that thesedevices are provided for illustrative purposes, and other devices may beemployed to perform the functionality disclosed herein without departingfrom the scope of the disclosure.

This disclosure describes some embodiments of the present technologywith reference to the accompanying drawings, in which only some of thepossible embodiments were shown. Other aspects may, however, be embodiedin many different forms and should not be construed as limited to theembodiments set forth herein. Rather, these embodiments were provided sothat this disclosure was thorough and complete and fully conveyed thescope of the possible embodiments to those skilled in the art.

Although specific embodiments are described herein, the scope of thetechnology is not limited to those specific embodiments. One skilled inthe art will recognize other embodiments or improvements that are withinthe scope and spirit of the present technology. Therefore, the specificstructure, acts, or media are disclosed only as illustrativeembodiments. The scope of the technology is defined by the followingclaims and any equivalents therein.

What is claimed is:
 1. A method for localization of an implanted markerwith ultrasound technology, the method comprising: emitting an array ofultrasonic sound waves from an ultrasonic transducer of an ultrasoundprobe; detecting reflected ultrasonic sound waves by the ultrasonictransducer, wherein the reflected ultrasonic sound waves include atleast a portion of the array of ultrasonic sound waves after beingreflected from a marker implanted proximate a lesion within an interiorof a patient; generating image data from the reflected ultrasonic soundwaves; analyzing, by a processor, the generated image data to identifythe marker within the interior of the patient; displaying, on a display,an ultrasound image including the marker based on the reflectedultrasonic sound waves; and based at least in part on the identificationof the marker, emitting an audible sound, wherein the audible sound isbased on how close the marker is to a center of a field of view of theultrasound image displayed on the display.
 2. The method of claim 1,further comprising varying a frequency or an intensity of a tone of theaudible sound.
 3. The method of claim 1, wherein prior to the emissionof the audible sound, determining, by the processor, at least one of adistance or an orientation to the marker, and wherein the emission ofthe audible sound is further based on the at least one determineddistance or orientation to the marker.
 4. The method of claim 3, furthercomprising varying a frequency or an intensity of a tone of the audiblesound based on the at least one determined distance or orientation tothe marker.
 5. The method of claim 3, further comprising guiding anincision instrument to the marker, by the emitted audible sound, basedon the at least one determined distance or orientation to the marker. 6.The method of claim 3, wherein the at least one determined distance ororientation to the marker is one of: a distance or an orientation from aportion of the ultrasound probe to the marker, or a distance or anorientation from a portion of an incision instrument to the marker. 7.The method of claim 6, further comprising indicating an incision pointon the patient for the incision instrument based on the distance or theorientation from a portion of the incision instrument to the marker. 8.The method of claim 6, further comprising indicating, on the display, avector path towards the marker for the incision instrument based on thedistance or the orientation from a portion of the incision instrument tothe marker.
 9. The method of claim 3, further comprising displaying, onthe display, the at least one determined distance or orientation to themarker.
 10. The method of claim 1, wherein the ultrasound probe emitsthe audible sound.
 11. A system for ultrasound localization, the systemcomprising: a marker, wherein the marker is configured to be implantedin an interior of a patient; an ultrasound probe comprising anultrasonic transducer, the ultrasonic transducer configured to emit anarray of ultrasonic sound waves and detect reflected ultrasonic soundwaves, wherein the reflected ultrasonic sound waves include at least aportion of the array of ultrasonic sound waves after being reflectedfrom the marker implanted proximate a lesion within the interior of thepatient; at least one output device configured to emit an audible sound,the at least one output device including a display; at least oneprocessor operatively connected to the at least one output device andthe ultrasound probe; and memory, operatively connected to the at leastone processor, storing instructions that when executed by the at leastone processor perform a set of operations comprising: generating imagedata from the reflected ultrasonic sound waves; analyzing, by the atleast one processor, the generated image data to identify the markerwithin the interior of the patient; displaying, on the display, anultrasound image including the marker based on the reflected ultrasonicsound waves; and based at least in part on the identification of themarker, emitting an audible sound via the at least one output device,wherein the audible sound is based on how close the marker is to acenter of a field of view of the ultrasound image displayed on thedisplay.
 12. The system of claim 11, wherein the at least one processorvaries a frequency or an intensity of a tone of the audible soundemitted from the at least one output device.
 13. The system of claim 11,wherein the set of operations that the at least one processor performsfurther comprises, prior to the emission of the audible sound,determining at least one of a distance or an orientation to the marker,and wherein the emission of the audible sound from the at least oneoutput device is further based on the at least one determined distanceor orientation to the marker.
 14. The system of claim 13, wherein the atleast one processor varies a frequency or an intensity of a tone of theaudible sound based on the at least one determined distance ororientation to the marker.
 15. The system of claim 13, furthercomprising an incision instrument configured for use within the interiorof the patient, wherein the set of operations that the at least oneprocessor performs further comprises guiding the incision instrument tothe marker, by the emitted audible sound, based on the at least onedetermined distance or orientation to the marker.
 16. The system ofclaim 13, further comprising an incision instrument configured for usewithin the interior of the patient, and wherein the at least onedetermined distance or orientation to the marker is one of: a distanceor an orientation from a portion of the ultrasound probe to the marker,or a distance or an orientation from a portion of the incisioninstrument to the marker.
 17. The system of claim 16, wherein the set ofoperations that the at least one processor performs further comprisesindicating an incision point on the patient for the incision instrumentbased on the distance or the orientation from a portion of the incisioninstrument to the marker.
 18. The system of claim 16, wherein the set ofoperations that the at least one processor performs further comprisesindicating, on the display, a vector path towards the marker for theincision instrument based on the distance or the orientation from aportion of the incision instrument to the marker.
 19. The system ofclaim 13, wherein the display is configured to indicate the at least onedetermined distance or orientation to the marker.
 20. The system ofclaim 11, wherein the ultrasound probe comprises the at least one outputdevice.
 21. The system of claim 11, wherein the marker is a radial-spokemarker, a multi-layered marker, or a fibrous polymer marker having atleast an ultrasound activated contrasting agent.